The Genomics of Inoperable Cancer. Neil Watkins

Size: px
Start display at page:

Download "The Genomics of Inoperable Cancer. Neil Watkins neil.watkins@monash.edu"

Transcription

1 The Genomics of Inoperable Cancer Neil Watkins

2 Surgical Bias in Cancer Genome Studies Surgical Specimens Lots of fresh tissue Snap frozen Consent is straightforward QC: Select for high quality, tumor rich areas Estimate stromal component Surgical Bias Early stage disease Tumors that can be accessed by surgery Tumors that can be cured by surgery alone Examples Lung cancer Mesothelioma

3 Lung Cancer Victorian Cancer Deaths 18% suitable for surgery Lung Colorectal Prostate Breast Pancreas Leukemia Lymphoma Stomach CNS MVA 20% suitable for radical chemo-radiation Huge at-risk population Lack of effective screening Increasing incidence in neversmoking women Deaths Per Annum New targeted therapies

4 Lung Cancer The many faces of lung cancer Adenocarcinoma Tries to make glands Squamous Cell Tries to make skin Large Cell Undifferentiated Small Cell Tries to make neurons and endocrine cells

5 Small Cell Lung Cancer Biology and genetics Primitive Neuroendocrine Phenotype 20% of all lung cancer Smoking related p53 and Rb mutations Highly chemosensitive Lethal recurrence in >90% of cases Widely metastatic 80% Locally advanced 20% Operated on by accident

6 Small Cell Lung Cancer Genomics Rudin et al, Nat Genet, 2012; 44: resected cases and matched normal 17 cell lines and germline controls 23 cell lines without germline controls Peiffer et al, Nat Genet, 2012; 44: SCLC out of 6,600 resected cases 63 SNP arrays 2 WGS 27 exomes 15 transcriptomes

7 Small Cell Lung Cancer Alternative approaches Percutaneous or endobronchial biopsy Genetically modified mouse models EBUS Patient derived xenografts Vinod Ganju, Alamgeer Muhammad

8 Mouse Model of SCLC Gene Targeting in Airway Epithelium Inhaled Cre-Recombinase Rblox/lox p53lox/lox Cre Recombinase Meuwissen et al, Cancer Cell, 2003 Anette Szczepny

9 EBUS-TBNA Endobronchial Ultrasound-Transbronchial Needle Aspiration Excellent DNA/RNA LN Met Genetic progression model Primary Fernando Rossello, Kieren Marini Tracy Leong, Dan Steinfort, Lou Irving

10 Patient-Derived Xenografts Direct from untreated patient to mouse DNA RNA DNA Snap Freeze Purify Blood Purify NSG Mouse Nude Mice Cell Line Cryopreserve Cryopreserve Anette Szczepny, Tracy Leong, Sam Jayasekara

11 Patient-Derived Xenografts SCLC (LX22) Gene expression profiling (Daniel et al, Cancer Res, 2008) Cancer stem cells (Liung et al, Cancer Res, 2008) BCL2 inhibitors (Hann et al, Cancer Res, 2008) Hh inhibitors (Park et al, Nat Med, 2011) SCLC Next generation sequencing Separation of mouse and human transcripts in silico

12 Patient-Derived Xenografts Genomics: Mouse vs Human Exon Capture Raw Reads 100% Align Human Genome Mapped 94% Unmapped 6% Align Mouse Genome Align Mouse Genome Unique Human 90 % Homologus 4.0 % Unique Mouse 1.0 % Unmapped 5.0 % RNA Seq Raw Reads 100% Align Human Genome SCLC Mapped 87% Unmapped 13% Align Mouse Genome Align Mouse Genome Unique Human 84 % Homologus 3.0 % Unique Mouse 9% Unmapped 4.0 % Whole Genome Raw Reads 100% Align Human Genome Mapped 75% Unmapped 25% Align Mouse Genome Align Mouse Genome Unique Human 73 % Homologus 2.0 % Unique Mouse 20.0 % Unmapped 5.0 % Rosello et al, PloSOne in press

13 Patient-Derived Xenografts Genomics: Human SCLC Rosello et al, PloSOne in press

14 Patient-Derived Xenografts Acquired Chemoresistance in SCLC Acquired Cis-Platinum Chemo Luciano Martelotto, Fernando Rossello, Kieren Marini

15 Patient-Derived Xenografts Acquired Chemoresistance in SCLC Chemo Regeneration Chemo Regeneration!! Chemo Regeneration Chemo Regeneration Naive Resistant? Luciano Martelotto, Fernando Rossello, Kieren Marini

16 Mesothelioma Biology Caused by asbestos

17 Mesothelioma Homozygous Deletions NF2 CDKN2A Genetic mouse model Nf2 Cancer lox/lox Cell Cdkn2a lox/lox A Somatic Sporadic Murine Mesothelioma Model Intrathoracic Adenoviral Cre recombinase Figure 7. Noninvasive Follow-Up of Spontaneous Murine MM Development (A) After crossing in a luciferase reporter allele (LucR), we followed MM development in both Nf2 F/F ;p53 F/F and Nf2 F/F ;p53 F/F ;Ink4a* / * mice noninvasively. An example of a bioluminescent primary tumor is shown at 9 weeks after IT injection of Adeno-Cre virus. (B) A LucR + clonal cell line derived from the primary tumor shown in (A) gave LcR + tumors upon orthotopic grafting into syngeneic hosts. Upon histological examination on H&Estained sections, both primary (C) and orthotopic tumor (D) showed the same invasive growth characteristics (invasive growth into thoracic wall, tw; vertebrae, v). Bars for different magnifications are shown as burn in marks (Axiocam, Color-CCD camera). expression of Cre recombinase via intrathoracic Adeno-Cre injection in mice. We used homozygously floxed conditional single (Nf2, Ink4a/Arf, and p53) and compound Nf2;Ink4a/Arf, Nf2;p53, and Nf2;p53;Ink4a* / * alleles and heterozygously floxed littermates. Although a range of different tumors were found in the conditional mutants due to either infection of tissues other than Jongsma et al Cancer Cell 2008 invasive in both parietal and visceral pleura, this in contrast to the tumors induced in Nf2 F/F ;p53 F/F mice. We conclude that Ink4a loss confers a more aggressive invasive phenotype to murine MM. Whereas in humans a preponderance of the epithelial type of MM opposed to sarcomatoid and mixed type is found, the

18 Mesothelioma Challenges Rarely resected Small biopsies or pleural fluid Intense fibrous and macrophage infiltration

19 Mesothelioma Bueno et al Plos One 2010

20 current therapies 2 and associated primarily with widespread com- Mesothelioma mesothelioma Ronglai Shenwho 6, Adam could be Olshen targeted 6, Valerie for early Rusch intervention. 2 & Marc Ladanyi Array-comparative 1,7 genomic hybridization (CGH) analysis of LETTERS two tumors (one per family) uncovered alterations encompassing Malignant mesotheliomas pleural mesotheliomas are aggressive (MPMs) tumors often that show are resistant CDKN2A to or presumed adjacent to drivers the BAP1 for the locus former at 3p21.1. two are CDKN2A In one tumor, and NF2, W-III-06T respectively, indicates the gene tumor ), genes a transition whose loss in drives copy number selection occurred for 3p21 at deletions or near and NF2 inactivation, but other highly recurrent mutations (T mercial have not use been of asbestos described. in the To identify twentieth additional century 3 8 driver. Approximately genes, the have BAP1 not been promoter, identified whereas despite in the prior second, efforts L-III-18T, 3. To refine a focal the deletion definition of candidate BAP1 regions, resided we within also analyzed a larger the deletion data using (Fig. the 2a). RAE We 27 we million used an US integrated workers were genomic exposed analysis to asbestos of 53 from MPM 1940 tumor to 1979, encompassing and samples more to thereafter guide a 4. focused In the United sequencing States, mesothelioma effort that uncovered incidence in also algorithm, performed a method linkage that studies assigns on statistical germline significance DNA from to each CNAs family. in a different somatic inactivating states varies from mutations 1 2/100,000 in BAP1 to 15/100,000 in 23% of MPMs. depending on In given a joint set of parametric cancer samples analysis (Fig. of the 1). two Genes families, within the significant largest linkage CNAs the The quantities BAP1 nuclear of asbestos deubiquitinase used, with ~3,000 is known deaths to target nationally histones per year. peak, as defined reaching by the a RAE maximum analysis lod were score reviewed of 2.1, for occurred biological at plausibility as oncogenic drivers. Fig. 1). Although We also integrated the region Affymetrix implicated expression in linkage 3p21 22 Despite (together asbestos with ASXL1 abatement as a efforts, Polycomb mesothelioma repressor rates subunit) have remained and (Supplementary LETTERS stable the HCF1 in the transcriptional United States co-factor, since 1994 and we are show expected that to BAP1 increase analyses, array data which on these assumed cases 4 that as an only additional those with tool mesothelioma for gene selection, were by knockdown 5 10% per in year MPM in cell Europe lines over affects the E2F next and 25 years Polycomb 5 7. A target marked affected, particularly was large in broader and included areas many of gain genes, or loss, a much where smaller identifying region was a increase genes. These in mesothelioma findings implicate is predicted transcriptional in developing deregulation countries, where in implicated single or a by few the driver array-cgh genes by analysis, including of CNAs a alone genomic has imbalance traditionally proven difficult. Using these approaches, we compiled a list of 25 the pathogenesis of MPM. Germline BAP1 mutations predispose potential driver genes to for sequencing in our 53 MPM tumors. Among malignant 1 Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. mesothelioma 2 Department of Medicine, University of Chicago, Chicago, Illinois, USA. 3 MPM, an aggressive neoplasm of serosal lining of chest etiologically Saudi linked Arabia. to asbestos, 5 Department is diagnosed of Chemical and in approximately Biochemical Engineering, 2,000 to University the highest of Iowa, rate Iowa of City, non-synonymous Iowa, USA. 6 New York mutations University, was Langone BAP1 Medical (in 12/53 Department of Human Genetics, University of Chicago, Chicago, Illinois, USA. 4 the mutations thus identified (Supplementary Table 1), the gene with Earth Sciences Department, King Fahd University of Petroleum and Minerals, Dhahran, Center 3,000 and individuals Cancer Center, annually New York, in the New United York, USA. States, 7 Mesothelioma most of whom Applied Research die MPMs; Foundation, 23%) Alexandria, (Supplementary Virginia, USA. Table 8 University 2), located of Hawaii at the Cancer epicenter Center, of University of Hawaii at Joseph R Testa 1 Manoa, Honolulu, Hawaii,, Mitchell Cheung 1 USA., Jianming 9 Department of Pei 1 Molecular Biosciences and, Jennifer E Below 2 Bioengineering, University, Yinfei Tan 1 of Hawaii at Manoa, Honolulu,, Eleonora Sementino 1 Hawaii, within 2 years of diagnosis. Studies of MPM have identified only two 3p21.1 losses seen in 30% of MPMs (Fig. 2). We detected only one USA. 10 Department of Pathology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA. Correspondence should be, addressed to J.R.T. frequent genetic Nancy J Cox 2,3 alterations, or M. the Carbone most common, A Umran Dogan 4,5 being homozygous, Harvey I Pass 6 silent somatic, Sandra Trusa 6 mutation in BAP1,, Mary Hesdorffer 7 representing a, Masaki Nasu 8,9 very high ratio of LETTERS 9p21 deletions, Amy Powers 8 centered on CDKN2A,, Zeyana Rivera 8,9 seen in up to 72% of tumors, Sabahattin Comertpay 8,9 non-synonymous, Mika Tanji 8,9 to synonymous somatic, Giovanni Gaudino 8 mutations. BAP1 (encoding Received 6 May; accepted 27 July; published online 28 August 2011; doi: /ng.912 and over 80% of MPM cell lines 1. Other recent studies have implicated BRCA1-associated protein 1) encodes a ubiquitin, Haining COOH-terminal Yang 8,10 & Michele NF2 loss through Carbone monosomy Germline 8 22 or 22q deletions as another common hydrolase originally identified through its interaction with BRCA1 event BAP1 mutations predispose to 2. Aside from these two tumor suppressors, other driver genes in (ref. 5). Sequencing also confirmed frequent inactivating mutations 1022 VOLUME 43 NUMBER 10 OCTOBER 2011 NATURE GENETICS MPM remain obscure. Here we used an integrated genomics approach in NF2 (11/53; 21%) and identified previously Because only a small fraction of asbestos-exposed individuals asbestos usage is increasing exponentially develop malignant mesothelioma mesothelioma 8 undescribed missense. Erionite shares physical to define recurrent genomic copy number 1 alterations (CNAs) in MPM mutations in LATS2 (2/53; 3.8%) and LATS1 (2/53; 3.8%). Notably,, and because mesothelioma characteristics with asbestos and also causes mesothelioma 1. With and to select candidates for sequencing. other common tumor suppressors (RB1, PTEN, RASSF1 and TP53) clustering is observed in some families, we searched for genetic increased urban development, exposure also occurs from disturbance We profiled CNAs predisposing Joseph R Testa factors. 1 in 53 primary MPM, Mitchell We discovered Cheung germline 1 tumor samples on, Jianming mutations Peiin 1 Agilent showed few, Jennifer of E asbestos- Below 2 or no mutations, and, Yinfei erionite-containing Tan 1 consistent, Eleonora soil 9,10 with previous Sementino. 1 studies in 244K CGH arrays., the gene encoding Nancy J Cox 2,3 Unsupervised clustering BRCA1 associated protein-1, A Umran Dogan 4,5 of the copy number (BAP1) in, Harvey I Pass 6 data MPM. We Some, Sandra Trusa 6 also identified a SMARCB1 individuals develop mesothelioma, Mary Hesdorffer 7 nonsense mutation following, Masaki Nasu 8,9 in a tumor exposure to LETTERS identified two major clusters, with most MPMs (41/53; 77%) showing with normal NF2 and BAP1., two families with Amy Powers 8 a high incidence, Zeyana Rivera 8,9 of mesothelioma, and we observed somatic, Sabahattin Comertpay 8,9 small amounts, Mika Tanji 8,9 of asbestos, whereas others, Giovanni Gaudino 8 exposed to heavy amounts a predominance of losses, whereas in a minority of MPMs (12/53; In all,, Haining Yang 8,10 & Michele Carbone 8 alterations affecting BAP1 in familial do not 1 42% of MPM tumors harbored either BAP1 loss, mutation 23%), genomic gains predominated (Supplementary Fig. 1). Based or both.. We BAP1 have losses reported were mesothelioma confirmed by clustering fluorescent in in some situ US hybridization (FISH) and mesotheliomas, on the analysis of indicating minimal common biallelic inactivation. regions of CNA, In addition the three most Turkish families in which up to 50% of members developed mesothelioma to mesothelioma, some BAP1 mutation carriers developed BAP1 uveal Because melanoma. mutations only a small We fraction also found of predispose asbestos-exposed germline BAP1 mutations individuals to 11 (Fig. 2) and were also found in 6 of 25 MPM cell common The deletions nuclear were 9p21, deubiquitinase 22q and 3p21. Although the known BAP1 lines (24%;. Supplementary This commonly incidence Fig. far exceeds 2). We confirmed that observed the frequency in cohorts of exposed asbestos to usage high is levels increasing of asbestos exponentially (4.6%). 8. Erionite shares physical 2 develop of 26 sporadic malignant mesotheliomas; both 1, and individuals because mesothelioma with mutant characteristics Over the past with 14 asbestos years, we and prospectively also causes studied mesothelioma families 1. With with inactivated by somatic mutations and 3p21.1 losses in BAP1 clustering 1 Department were of is previously Pathology, Memorial observed in diagnosed Sloan-Kettering some families, with uveal Cancer we searched melanoma. Center, New for We York, New York, genetic high USA. increased incidence urban of development, mesothelioma exposure to identify also occurs putative from mesotheliomasusceptibility of asbestos- and genes. erionite-containing We focused two soil 9,10 US. mesothelioma families, disturbance also predisposing observed factors. somatic We truncating discovered BAP1 germline mutations mutations and aberrant in malignant pleural mesothelioma 2 Department of Surgery, Memorial Sloan-Kettering Cancer Center (MSKCC), New York, New York, USA. 3 Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 4 National Centre for Asbestos Disease Research, School of Medicine and Pharmacology, University of Western Australia, Sir Charles Gairdner Hospital, Nedlands, Australia. 5 Department itchell Cheung BAP1 the of Radiation gene expression 1, encoding Oncology, Jianming in Memorial BRCA1 sporadic Pei 1 associated Sloan-Kettering, Jennifer mesotheliomas protein-1 Cancer E Below without Center, (BAP1) 2 New, Yinfei germline York, New Tan 1 York,, Eleonora one USA. Some in 6 Wisconsin Epidemiology-Biostatistics, Sementino individuals (W family) develop 1, and Memorial mesothelioma one in Sloan-Kettering Louisiana following (L family), Cancer exposure Center, in which to mutations. two New York, families with a high incidence of mesothelioma, and small amounts of asbestos, whereas others exposed to heavy amounts mran Dogan 4,5 New These York, USA. results identify, Harvey I 7 Human Pass 6 Oncology a BAP1-related & Pathogenesis, Sandra Trusa 6 cancer Program, syndrome Memorial Sloan-Kettering, Mary Hesdorffer 7 members were Cancer neither Center,, Masaki Nasu 8,9 New exposed York, New to York, erionite USA. nor Correspondence had occupational should be addressed to M.L. that we Matthew observed somatic alterations affecting BAP1 in familial do not 1. We have reported mesothelioma clustering in some US and na Rivera mesotheliomas, 8,9 is characterized Bott 1,2, by Marie mesothelioma Brevet 1, Sabahattin indicating Comertpay biallelic 8,9, and Barry uveal S Taylor melanoma. 3 We hypothesize that other cancers may inactivation., Mika also be Tanji involved In 8,9, Shigeki Shimizu exposure addition, Giovanni and Gaudino Turkish families 8 to 1, Tatsuo asbestos, Ito thus 1, removing Lu, Haining which Yang up 8,10 Wang 1, confounding Jenette Creaney factor of 4, heavy Received Richard 3 November A Lake2010; 4, Maureen accepted 16 F May Zakowski 2011; published 1, Boris online Reva 5 June 3, 2011; Chris exposure doi: /ng.855 Sander to 3 carcinogens, Robert Delsite known to 5 to,& 50% Simon cause of members a Powell high incidence developed 5, Qin of Zhou meso- 6, that to mesothelioma, some predominates mutation upon asbestos carriers developed exposure. thelioma. 11 Family. This members incidence developed far exceeds various that malignancies, observed in although cohorts Germline Ronglai Shen 6, Adam BAP1 Olshen 6, Valerie mutations Rusch 2 & Marc predispose Ladanyi 1,7 to These uveal melanoma. findings will We help also to found identify germline individuals BAP1 at mutations high risk of in mesothelioma exposed to high predominated levels of asbestos (Fig. 1a,b (4.6%). and Supplementary Table 1). 668 raction of mesothelioma 2 asbestos-exposed of 26 sporadic who mesotheliomas; individuals could be targeted both asbestos for individuals early usage intervention. with is increasing mutant exponentially Array-comparative Over the 8 VOLUME 43 NUMBER 7 JULY 2011 NATURE GENETICS. Erionite past 14 shares years, genomic physical we prospectively hybridization studied (CGH) families analysis with of sothelioma BAP1 malignant Malignant 1, and were because previously pleural mesotheliomas mesothelioma diagnosed with (MPMs) characteristics uveal often melanoma. show with We CDKN2A asbestos and two high or presumed also tumors incidence causes (one drivers mesothelioma of per mesothelioma for family) the former 1. uncovered With to two identify are alterations CDKN2A putative and mesotheliomasusceptibility encompassing NF2, respectively, the gene in some families, Malignant also and observed NF2 inactivation, we mesotheliomas searched somatic for truncating but other genetic are aggressive BAP1 highly increased tumors mutations recurrent urban that and mutations are development, aberrant resistant to exposure or adjacent also occurs to genes. or genes the from BAP1 We whose disturbance focused loss locus at on drives 3p21.1. two US selection In mesothelioma for 3p21 deletions one tumor, W-III-06T families, e discovered current BAP1 have germline expression not been described. therapies mutations 2 in and sporadic To associated in mesotheliomas identify additional primarily of asbestos- without driver widespread and germline genes, erionite-containing commercial mutations. (T one have indicates not soil Wisconsin 9,10 been identified. tumor ), (W family) despite a transition and one prior in copy in Louisiana efforts number 3. To (L refine occurred family), the at in definition of candidate Joseph R Testa 1, Mitchell Cheung 1, Jianming Pei 1, Jennifer E Below 2, Yinfei Tan 1, Eleonora Sementino 1, or which near A1 associated we used an protein-1 use These integrated of asbestos (BAP1) results genomic in in identify the twentieth a analysis BAP1-related of 53 Some century individuals 3 8 MPM cancer tumor. Approximately syndrome develop mesothelioma members BAP1 promoter, were following neither regions, whereas exposure exposed we also in the to analyzed second, erionite the L-III-18T, nor data had using a focal occupational the RAE Nancy deletion h incidence 27 that samples J million of is mesothelioma, characterized to Cox guide 2,3, a A focused Umran US workers by and were mesothelioma sequencing Dogan 4,5, exposed to small asbestos and effort Harvey amounts uveal that I from melanoma. uncovered Pass 6, Sandra of 1940 asbestos, 1979, whereas encompassing exposure algorithm, Trusa 6, Mary others to a exposed asbestos, method Hesdorffer BAP1 heavy resided thus that assigns 7, removing statistical Masaki amounts within the a larger confounding significance Nasu 8,9, deletion factor to CNAs (Fig. of 2a). heavy in a Amy We lterations and We somatic Powers affecting hypothesize inactivating 8, Zeyana more thereafter BAP1 that in 4 familial. In other mutations Rivera United cancers in 8,9 States, may BAP1, Sabahattin do mesothelioma also not 1 23%. be We involved of Comertpay MPMs. 8,9, have incidence reported and mesothelioma in also exposure given Mika set Tanji performed clustering to of carcinogens cancer 8,9, Giovanni samples linkage some studies known (Fig. Gaudino US on and to 1). germline cause Genes 8, Haining a high within DNA incidence significant Yang 8,10 from each of family. mesothelioma. CNAs & ting biallelic different that Michele The inactivation. mesothelioma BAP1 Carbone nuclear states varies In predominates deubiquitinase 8 addition from 1 2/100,000 upon is known Turkish to asbestos to target 15/100,000 families exposure. histones depending which on up to In as defined 50% a joint of members parametric Family by the members RAE analysis developed analysis developed were reviewed mesothelioma deaths 11 at of the two various families, malignancies, for biological plausibility as oncogenic the largest although linkage e BAP1 mutation the These (together quantities findings with carriers of will ASXL1 asbestos developed help as used, to a identify Polycomb with ~3,000 individuals repressor subunit) nationally. high This risk and incidence per of year. far peak, mesothelioma exceeds reaching that predominated drivers. We observed a maximum cohorts (Fig. also lod score 1a,b integrated and of 2.1, Supplementary Affymetrix expression occurred at Table 3p ). lso found Despite mesothelioma Because the HCF1 transcriptional germline asbestos only BAP1 a who small abatement mutations could fraction be co-factor, efforts, in targeted of asbestos-exposed and mesothelioma exposed for early we show rates intervention. that BAP1 array high individuals have levels remained of asbestos (Supplementary asbestos (4.6%). Array-comparative data usage on is these increasing cases Fig. 1). genomic Although 4 as exponentially an hybridization additional tool the region 8. Erionite implicated (CGH) for shares gene analysis selection, in physical linkage of knockdown in MPM cell lines affects E2F and Polycomb target theliomas; stable develop both individuals malignant the United with mesothelioma States mutant since , and and Over because are expected the mesothelioma past 14 to increase years, we prospectively analyses, characteristics two particularly tumors which (one in broader studied with assumed per asbestos families family) areas that and uncovered of gain or only with also those causes alterations loss, where with mesothelioma encompassing identifying 1. With a were

21 Mesothelioma LETTERS gains effective e) and ce s) of ght and left, al position Green lines toff for.1, FDR = ing are (CDKN2A, s not < <10 7 CHD5 ERFFI1 SDHB RAP1A BAP1 RASSF1 DUSP7 dent collectations, 18%) in MPM cell plementary 1 mutations mutations, 5 missense mutations, 13 tions at or near splice sites (Fig. 3). Of rs, we confirmed the mutations to be atched normal tissue available. The tions are predicted to result in loss of d/or the C-terminal protein binding emistry (IHC) for BAP1 on paraffin- 3 MPM tumors from the original 1 2 RICTOR TRIO 3 4 PTPN LATS1 7 RHEB 8 PTPRD 9 10 PTEN RB LATS2 ING1 SPRY2 CDKN3 material containing five different splice site mutations, we confirmed that four of the five mutations resulted either in partially retained introns or missing exons (Supplementary Table 5), leading to abnormal stop codons just downstream. To assess whether BAP1 missense mutations (resulting in p.ser63cys, p.ala95asp and p.cys91trp) were functionally Bott et al Nat Genet 2011 abnormal, we purified FLAG-tagged mutant proteins by immunoprecipitation and subjected them to an in vitro enzymatic assay (Online Methods) in 293T cells and in two BAP1-null MPM cell lines (H28, TP STK SMARCB1 CHEK2 DMC1 NF

22 Mesothelioma Patient-derived xenograft WGS+RNAseq SNV/InDel Exonic Non Synonymous Stop Gained Stop lost Frameshift Critical Splice Allele frequency >0.33 Allele frequency >0.33 Allele frequency >0.33 Allele frequency >0.33 SIFT<0.05 Mutant allele expressed Mutant allele expressed Mutant allele expressed Mutant allele expressed WT allele expressed Y N WT allele expressed Y N WT allele not expressed WT allele expressed Y N Candidate gain of function Candidate loss of function Candidate gain of function Candidate loss of function Candidate loss of function Candidate gain of function Candidate loss of function Fernando Rossello

23 Acknowledgements: USA Watkins lab Craig Peacock Dave Wang Wendy Devereux Jonathon Rhodes Scott Burkholder Tom Harcke Vincent Daniel Kabilar Gunilan Greg Gesell Ian Corcoran-Schwartz Kim Briggs Chris Nelson Robert Beaty Jared Hierman Neal Copeland Adam Dupuy David Berman Charles Eberhart Bill Matsui Phil Beachy Steve Baylin Julien Sage Kwon Park Bill Sellers Silvia Buonomici Michael Taylor Julien Sage Luigi Marchionni NCI/Lung SPORE NIH/NINDS Children s Brain Tumor Foundation FAMRI Kimmel Cancer Foundation Commonwealth Foundation

24 Acknowledgements: Australia Watkins lab- present Jason Cain Anette Sczepny Sam Jayasekara Amali Mudiyanselage Lisa McKenzie Keiren Marini Fernando Rossello Aneta Strzlecki Tracy Leong Dean Popovski Sandra O Toole Alex Swarbrick Monash Microimaging Richard Tothill Jason Li Geoff McCaughan Prue Russell Dan Steinfort Lou Irving Watkins lab- emeritus Nancy D Cruz Peter Morris Brendan Payne Luciano Martelotto Andrew McCaw VCA NHMRC

Breast cancer and the role of low penetrance alleles: a focus on ATM gene

Breast cancer and the role of low penetrance alleles: a focus on ATM gene Modena 18-19 novembre 2010 Breast cancer and the role of low penetrance alleles: a focus on ATM gene Dr. Laura La Paglia Breast Cancer genetic Other BC susceptibility genes TP53 PTEN STK11 CHEK2 BRCA1

More information

Mesothelioma. Mesothelioma and Asbestos 11/21/2009

Mesothelioma. Mesothelioma and Asbestos 11/21/2009 Mesothelioma Michele Carbone, M.D.,PH.D. Director Cancer Research Center of Hawaii Professor and Chairman, Dept. of Pathology J.A. Burns Medical School University of Hawaii Honolulu, HI 96813 Mesotheliomas

More information

MUTATION, DNA REPAIR AND CANCER

MUTATION, DNA REPAIR AND CANCER MUTATION, DNA REPAIR AND CANCER 1 Mutation A heritable change in the genetic material Essential to the continuity of life Source of variation for natural selection New mutations are more likely to be harmful

More information

BAP1 germline mutations A new Cutaneous Nevus Melanoma Syndrome. Thomas Wiesner

BAP1 germline mutations A new Cutaneous Nevus Melanoma Syndrome. Thomas Wiesner BAP1 germline mutations A new Cutaneous Nevus Melanoma Syndrome Thomas Wiesner Disclosure Listed as co-inventor US patent application US 61/463,389 BAP1 mutational analysis in determining susceptibility

More information

Griffith University - Case for Support. Mesothelioma Research Program

Griffith University - Case for Support. Mesothelioma Research Program Griffith University - Case for Support Mesothelioma Research Program Professor Lyn Griffiths Director, Dean, Research and Director, Genomics Research Centre (GHI) Established in 2007. Integrated health

More information

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function:

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function: Cancer is a genetic disease: Inherited cancer Sporadic cancer What is Cancer? Cancer typically involves a change in gene expression/function: Qualitative change Quantitative change Any cancer causing genetic

More information

Brigham and Women s Hospital, Boston, MA, USA; 2 Verastem, Inc., Boston, MA, USA

Brigham and Women s Hospital, Boston, MA, USA; 2 Verastem, Inc., Boston, MA, USA Determination of Biomarker Response in a Phase II Window of Opportunity Study of Defactinib (VS 6063), a Focal Adhesion Kinase (FAK) Inhibitor, in Patients with Resectable Malignant Pleural Mesothelioma

More information

Independent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens

Independent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens Independent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens Assunta De Rienzo, Ph.D. 1, Robert W. Cook, Ph.D. 2,

More information

بسم هللا الرحمن الرحيم

بسم هللا الرحمن الرحيم بسم هللا الرحمن الرحيم Updates in Mesothelioma By Samieh Amer, MD Professor of Cardiothoracic Surgery Faculty of Medicine, Cairo University History Wagner and his colleagues (1960) 33 cases of mesothelioma

More information

Targeted Therapy What the Surgeon Needs to Know

Targeted Therapy What the Surgeon Needs to Know Targeted Therapy What the Surgeon Needs to Know AATS Focus in Thoracic Surgery 2014 David R. Jones, M.D. Professor & Chief, Thoracic Surgery Memorial Sloan Kettering Cancer Center I have no disclosures

More information

Advances in Treatment of Malignant Pleural Mesothelioma: A Reason for Hope

Advances in Treatment of Malignant Pleural Mesothelioma: A Reason for Hope Advances in Treatment of Malignant Pleural Mesothelioma: A Reason for Hope Daniel H. Sterman, M.D. Associate Professor of Medicine and Surgery Co-Director, PENN Mesothelioma and Pleural Program University

More information

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma The Use of Kinase Inhibitors: Translational Lab Results Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma Sheelu Varghese, Ph.D. H. Richard Alexander, M.D.

More information

A 70-year old Man with Pleural Effusion

A 70-year old Man with Pleural Effusion Mesothelioma Diagnosis: Pitfalls and Latest Updates S Klebe and DW Henderson Recommendations Indisputable malignant cells on cytomorphological criteria which demonstrate a mesothelial phenotype, which

More information

Mesothelioma. 1995-2013, The Patient Education Institute, Inc. www.x-plain.com ocft0101 Last reviewed: 03/21/2013 1

Mesothelioma. 1995-2013, The Patient Education Institute, Inc. www.x-plain.com ocft0101 Last reviewed: 03/21/2013 1 Mesothelioma Introduction Mesothelioma is a type of cancer. It starts in the tissue that lines your lungs, stomach, heart, and other organs. This tissue is called mesothelium. Most people who get this

More information

Genetic Biomarkers of Risk in Toxic Tort Litigation. Gary Marchant, Arizona State University Kirk Hartley, LSP Group LLC

Genetic Biomarkers of Risk in Toxic Tort Litigation. Gary Marchant, Arizona State University Kirk Hartley, LSP Group LLC Genetic Biomarkers of Risk in Toxic Tort Litigation Gary Marchant, Arizona State University Kirk Hartley, LSP Group LLC The Genetic Era is (Finally) Here Genetics and Toxic Torts Two major types of data:

More information

Male. Female. Death rates from lung cancer in USA

Male. Female. Death rates from lung cancer in USA Male Female Death rates from lung cancer in USA Smoking represents an interesting combination of an entrenched industry and a clearly drug-induced cancer Tobacco Use in the US, 1900-2000 5000 100 Per Capita

More information

Malignant Mesothelioma State of the Art

Malignant Mesothelioma State of the Art Malignant Mesothelioma State of the Art Paul Baas The Netherlands Cancer Institute August 12, 2011, Carlsbad, CA Summary Diagnosis; epithelial type subdivided Pleiomorphic vs other Staging: IASLC-IMIG

More information

Gene mutation and molecular medicine Chapter 15

Gene mutation and molecular medicine Chapter 15 Gene mutation and molecular medicine Chapter 15 Lecture Objectives What Are Mutations? How Are DNA Molecules and Mutations Analyzed? How Do Defective Proteins Lead to Diseases? What DNA Changes Lead to

More information

Neoplasms. Review of Normal Cells. Bio 375 Pathophysiology

Neoplasms. Review of Normal Cells. Bio 375 Pathophysiology Neoplasms Bio 375 Pathophysiology Review of Normal Cells During its life span, each cell follows the basic cell cycle of growth and reproduction called mitosis The timing of each event varies with the

More information

Contents. molecular biology techniques. - Mutations in Factor II. - Mutations in MTHFR gene. - Breast cencer genes. - p53 and breast cancer

Contents. molecular biology techniques. - Mutations in Factor II. - Mutations in MTHFR gene. - Breast cencer genes. - p53 and breast cancer Contents Introduction: biology and medicine, two separated compartments What we need to know: - boring basics in DNA/RNA structure and overview of particular aspects of molecular biology techniques - How

More information

ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials)

ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials) ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials) 3 Integrated Trials Testing Targeted Therapy in Early Stage Lung Cancer Part of NCI s Precision Medicine Effort in

More information

Lung Cancer: More than meets the eye

Lung Cancer: More than meets the eye Lung Cancer Education Program November 23, 2013 Lung Cancer: More than meets the eye Shantanu Banerji MD, FRCPC Presenter Disclosure Faculty: Shantanu Banerji Relationships with commercial interests: Grants/Research

More information

1 page Overview. CONCURRENT 1D, 1E, 1F Biology & Pathogenesis Multi-Modality Immunology 1

1 page Overview. CONCURRENT 1D, 1E, 1F Biology & Pathogenesis Multi-Modality Immunology 1 1 page Overview 21 Oct Tuesday 1500 on REGISTRATION 1800 Welcome Reception & Cocktails at the Cape Town International Conference Centre (CTICC) 22 Oct Wednesday 0730 REGISTRATION 0830 OPENING 0900 PLENARY

More information

Mutations: 2 general ways to alter DNA. Mutations. What is a mutation? Mutations are rare. Changes in a single DNA base. Change a single DNA base

Mutations: 2 general ways to alter DNA. Mutations. What is a mutation? Mutations are rare. Changes in a single DNA base. Change a single DNA base Mutations Mutations: 2 general ways to alter DNA Change a single DNA base Or entire sections of DNA can move from one place to another What is a mutation? Any change in the nucleotide sequence of DNA Here

More information

Understanding Pleural Mesothelioma

Understanding Pleural Mesothelioma Understanding Pleural Mesothelioma UHN Information for patients and families Read this booklet to learn about: What is pleural mesothelioma? What causes it? What are the symptoms? What tests are done to

More information

Applications of comprehensive clinical genomic analysis in solid tumors: obstacles and opportunities

Applications of comprehensive clinical genomic analysis in solid tumors: obstacles and opportunities Applications of comprehensive clinical genomic analysis in solid tumors: obstacles and opportunities Vincent A. Miller, M.D. Foundation Medicine, Inc. AACR Annual Meeting 2012 Current Concepts session

More information

Prevalenza delle mutazioni TMEM127 nel feocromocitoma sporadico

Prevalenza delle mutazioni TMEM127 nel feocromocitoma sporadico Prevalenza delle mutazioni TMEM127 nel feocromocitoma sporadico Giuseppe Opocher Veneto Institute of Oncology and Department of Medical and Surgical Sciences, University of Padova, Italy Sympathetic paraganglia

More information

Principal Investigator: Valerie W. Rusch, MD, FACS, Chief, Thoracic Surgery Memorial Sloan-Kettering Cancer Center

Principal Investigator: Valerie W. Rusch, MD, FACS, Chief, Thoracic Surgery Memorial Sloan-Kettering Cancer Center Protocol 1101-1088 Phase I study of intra-pleural administration of GL-ONC1 in patients with malignant pleural effusion: primary, metastases and mesothelioma Principal Investigator: Valerie W. Rusch, MD,

More information

Lung Cancer: Diagnosis, Staging and Treatment

Lung Cancer: Diagnosis, Staging and Treatment PATIENT EDUCATION patienteducation.osumc.edu Lung Cancer: Diagnosis, Staging and Treatment Cancer begins in our cells. Cells are the building blocks of our tissues. Tissues make up the organs of the body.

More information

Personalized Treatment for Malignant Mesothelioma

Personalized Treatment for Malignant Mesothelioma Personalized Treatment for Malignant Mesothelioma RN Taub (Onc) J Chabot (Surg) A Borczuk (Path) J Sonnet (Surg) M Kluger (Surg) R Fawwaz (Nuc. Med) E Hare (Onc) Columbia University Mesothelioma Center

More information

Screening, early referral and treatment for asbestos related cancer

Screening, early referral and treatment for asbestos related cancer Screening, early referral and treatment for asbestos related cancer Marc de Perrot, MD, MSc, FRCSC Toronto Mesothelioma Research Program University of Toronto Asbestos related diseases Mesothelioma Lung

More information

CHAPTER 2: UNDERSTANDING CANCER

CHAPTER 2: UNDERSTANDING CANCER CHAPTER 2: UNDERSTANDING CANCER INTRODUCTION We are witnessing an era of great discovery in the field of cancer research. New insights into the causes and development of cancer are emerging. These discoveries

More information

YOUR LUNG CANCER PATHOLOGY REPORT

YOUR LUNG CANCER PATHOLOGY REPORT UNDERSTANDING YOUR LUNG CANCER PATHOLOGY REPORT 1-800-298-2436 LungCancerAlliance.org A GUIDE FOR THE PATIENT 1 CONTENTS What is a Pathology Report?...3 The Basics...4 Sections of a Pathology Report...7

More information

How Cancer Begins???????? Chithra Manikandan Nov 2009

How Cancer Begins???????? Chithra Manikandan Nov 2009 Cancer Cancer is one of the most common diseases in the developed world: 1 in 4 deaths are due to cancer 1 in 17 deaths are due to lung cancer Lung cancer is the most common cancer in men Breast cancer

More information

The Diagnosis of Cancer in the Pathology Laboratory

The Diagnosis of Cancer in the Pathology Laboratory The Diagnosis of Cancer in the Pathology Laboratory Dr Edward Sheffield Christmas Select 74 Meeting, Queen s Hotel Cheltenham, 3 rd December 2014 Agenda Overview of the pathology of cancer How specimens

More information

Primary -Benign - Malignant Secondary

Primary -Benign - Malignant Secondary TUMOURS OF THE LUNG Primary -Benign - Malignant Secondary The incidence of lung cancer has been increasing almost logarithmically and is now reaching epidemic levels. The overall cure rate is very low

More information

National Cancer Institute Research on Childhood Cancers. In the United States in 2005, approximately 9,510 children under age 15 will be

National Cancer Institute Research on Childhood Cancers. In the United States in 2005, approximately 9,510 children under age 15 will be CANCER FACTS N a t i o n a l C a n c e r I n s t i t u t e N a t i o n a l I n s t i t u t e s o f H e a l t h D e p a r t m e n t o f H e a l t h a n d H u m a n S e r v i c e s National Cancer Institute

More information

Lung cancer and asbestos

Lung cancer and asbestos Lung cancer and asbestos Bureau Veritas Training Bill Sanderson For the benefit of business and people To begin with.. There are known knowns, that is there are things we know that we know. There are known

More information

MALIGNANT PLEURAL FLUIDS AID MESOTHELIOMA CELL GROWTH AND PROPAGATION

MALIGNANT PLEURAL FLUIDS AID MESOTHELIOMA CELL GROWTH AND PROPAGATION MALIGNANT PLEURAL FLUIDS AID MESOTHELIOMA CELL GROWTH AND PROPAGATION HUI MIN CHEAH PhD Candidate School of Medicine and Pharmacology University of Western Australia Lung Institute of Western Australia

More information

Genetics and Breast Cancer. Elly Lynch, Senior Genetic Counsellor Manager, Austin Health Clinical Genetics Service

Genetics and Breast Cancer. Elly Lynch, Senior Genetic Counsellor Manager, Austin Health Clinical Genetics Service Genetics and Breast Cancer Elly Lynch, Senior Genetic Counsellor Manager, Austin Health Clinical Genetics Service Overview Background/Our Team What is the difference between sporadic/familial cancer? How

More information

This factsheet aims to outline the characteristics of some rare lung cancers, and highlight where each type of lung cancer may be different.

This factsheet aims to outline the characteristics of some rare lung cancers, and highlight where each type of lung cancer may be different. There are several different kinds of lung cancer, often referred to as lung cancer subtypes. Some of these occur more often than others. In this factsheet we will specifically look at the subtypes of cancers

More information

P L E U R A L M E S O T H E L I O M A

P L E U R A L M E S O T H E L I O M A For media outside the US, UK and Canada only P L E U R A L M E S O T H E L I O M A 1. Overview 2. What is pleural mesothelioma? 3. How common is pleural mesothelioma? 4. What are the risk factors for pleural

More information

Non Small Cell Lung Cancer: Scientific Discoveries and the Pursuit of Progress

Non Small Cell Lung Cancer: Scientific Discoveries and the Pursuit of Progress Non Small Cell Lung Cancer: Scientific Discoveries and the Pursuit of Progress Lung Cancer Accounts for 14% of All New Cancer Diagnoses in the United States 1 Lung cancer is the second most common malignancy

More information

L Lang-Lazdunski, A Bille, S Marshall, R Lal, D Landau, J Spicer

L Lang-Lazdunski, A Bille, S Marshall, R Lal, D Landau, J Spicer Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine and systemic chemotherapy in malignant pleural mesothelioma. A 10-year experience. L Lang-Lazdunski, A Bille, S Marshall, R Lal,

More information

Cancer: Genetic testing can save lives

Cancer: Genetic testing can save lives Cancer: Genetic testing can save lives Track chances of having a tumor's tendency among people with a history of disease cases in the family, but practice should not be trivialized and hurt even more who

More information

Mesothelioma. 1. Introduction. 1.1 General Information and Aetiology

Mesothelioma. 1. Introduction. 1.1 General Information and Aetiology Mesothelioma 1. Introduction 1.1 General Information and Aetiology Mesotheliomas are tumours that arise from the mesothelial cells of the pleura, peritoneum, pericardium or tunica vaginalis [1]. Most are

More information

Lecture 3: Mutations

Lecture 3: Mutations Lecture 3: Mutations Recall that the flow of information within a cell involves the transcription of DNA to mrna and the translation of mrna to protein. Recall also, that the flow of information between

More information

Varianti genetiche e interazione gene-asbesto nel mesotelioma pleurico

Varianti genetiche e interazione gene-asbesto nel mesotelioma pleurico Varianti genetiche e interazione gene-asbesto nel mesotelioma pleurico Tunesi Sara, Ferrante Daniela, Mirabelli Dario, Andorno Silvano, Betti Marta, Fiorito Giovanni, Guarrera Simonetta, Casalone Elisabetta,

More information

Fulfilling the Promise

Fulfilling the Promise Fulfilling the Promise Advancing the Fight Against Cancer: America s Medical Schools and Teaching Hospitals For more than a century, the nation s medical schools and teaching hospitals have worked to understand,

More information

Malignant Mesothelioma: an Update

Malignant Mesothelioma: an Update Malignant Mesothelioma: an Update Nico van Zandwijk Asbestos Diseases Research Institute Bernie Banton Centre University of Sydney Australia Physicians Week RACP 19-5-2009 Health Risks of Asbestos Fibers

More information

Clinical cases in Malignant Pleural Mesothelioma: Adherence to the ESMO Clinical Practice Guidelines

Clinical cases in Malignant Pleural Mesothelioma: Adherence to the ESMO Clinical Practice Guidelines Clinical cases in Malignant Pleural Mesothelioma: Adherence to the ESMO Clinical Practice Guidelines Wieneke Buikhuisen The Netherlands Cancer Institute Amsterdam The Netherlands Case (1) Male, 56 year

More information

Lessons learned from the Western Australian experience with mesothelioma

Lessons learned from the Western Australian experience with mesothelioma Lessons learned from the Western Australian experience with mesothelioma Alison Reid, Western Australian Institute for Medical Research In partnership with Nick de Klerk, Nola Olsen, Jan Sleith, Geoffrey

More information

H. Richard Alexander, Jr., M.D. Department of Surgery and The Greenebaum Cancer Center University of Maryland School of Medicine Baltimore, Md

H. Richard Alexander, Jr., M.D. Department of Surgery and The Greenebaum Cancer Center University of Maryland School of Medicine Baltimore, Md Major Advances in Cancer Prevention, Diagnosis and Treatment~ Why Mesothelioma Leads the Way H. Richard Alexander, Jr., M.D. Department of Surgery and The Greenebaum Cancer Center University of Maryland

More information

Diseases. Inflammations Non-inflammatory pleural effusions Pneumothorax Tumours

Diseases. Inflammations Non-inflammatory pleural effusions Pneumothorax Tumours Pleura Visceral pleura covers lungs and extends into fissures Parietal pleura limits mediastinum and covers dome of diaphragm and inner aspect of chest wall. Two layers between them (pleural cavity) contains

More information

Test Information Sheet

Test Information Sheet Test Information Sheet GeneDx 207 Perry Parkway Gaithersburg, MD 20877 Phone: 888-729-1206 Fax: 301-710-6594 E-mail: wecare@genedx.com www.genedx.com/oncology OncoGene Dx: High/Moderate Risk Panel Sequence

More information

Nuevas tecnologías basadas en biomarcadores para oncología

Nuevas tecnologías basadas en biomarcadores para oncología Nuevas tecnologías basadas en biomarcadores para oncología Simposio ASEBIO 14 de marzo 2013, PCB Jose Jimeno, MD, PhD Co-Founder / Vice Chairman Pangaea Biotech SL Barcelona, Spain PANGAEA BIOTECH BUSINESS

More information

Round Table with Drs. Anne Tsao and Alex Farivar, Case 2: Mesothelioma

Round Table with Drs. Anne Tsao and Alex Farivar, Case 2: Mesothelioma Round Table with Drs. Anne Tsao and Alex Farivar, Case 2: Mesothelioma I d like to welcome everyone, thanks for coming out to our lunch with experts. The faculty today are great people in the thoracic

More information

The Human Genome Project. From genome to health From human genome to other genomes and to gene function Structural Genomics initiative

The Human Genome Project. From genome to health From human genome to other genomes and to gene function Structural Genomics initiative The Human Genome Project From genome to health From human genome to other genomes and to gene function Structural Genomics initiative June 2000 What is the Human Genome Project? U.S. govt. project coordinated

More information

Lung Cancer: Diagnosis, Staging and Treatment

Lung Cancer: Diagnosis, Staging and Treatment PATIENT EDUCATION patienteducation.osumc.edu Lung Cancer: Diagnosis, Staging and Treatment Cancer starts in our cells. Cells are the building blocks of our tissues. Tissues make up the organs of the body.

More information

What is New in Oncology. Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals

What is New in Oncology. Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals What is New in Oncology Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals Personalized Medicine Personalized Genomics Genomic Medicine Precision Medicine Definition Application

More information

Individualizing Your Lung Cancer Care: Informing Decisions Through Biomarker Testing

Individualizing Your Lung Cancer Care: Informing Decisions Through Biomarker Testing Individualizing Your Lung Cancer Care: Informing Decisions Through Biomarker Testing These Are Hopeful Times for Lung Cancer Survivors When people first learn they have cancer, they are often afraid. But

More information

1 Mutation and Genetic Change

1 Mutation and Genetic Change CHAPTER 14 1 Mutation and Genetic Change SECTION Genes in Action KEY IDEAS As you read this section, keep these questions in mind: What is the origin of genetic differences among organisms? What kinds

More information

Lung Cancer. Public Outcomes Report. Submitted by Omar A. Majid, MD

Lung Cancer. Public Outcomes Report. Submitted by Omar A. Majid, MD Public Outcomes Report Lung Cancer Submitted by Omar A. Majid, MD Lung cancer is the most common cancer-related cause of death among men and women. It has been estimated that there will be 226,1 new cases

More information

Objectives. Mylene T. Truong, MD. Malignant Pleural Mesothelioma Background

Objectives. Mylene T. Truong, MD. Malignant Pleural Mesothelioma Background Imaging of Pleural Tumors Mylene T. Truong, MD Imaging of Pleural Tumours Mylene T. Truong, M. D. University of Texas M.D. Anderson Cancer Center, Houston, TX Objectives To review tumors involving the

More information

LESSON 3.5 WORKBOOK. How do cancer cells evolve? Workbook Lesson 3.5

LESSON 3.5 WORKBOOK. How do cancer cells evolve? Workbook Lesson 3.5 LESSON 3.5 WORKBOOK How do cancer cells evolve? In this unit we have learned how normal cells can be transformed so that they stop behaving as part of a tissue community and become unresponsive to regulation.

More information

Update on Mesothelioma

Update on Mesothelioma November 8, 2012 Update on Mesothelioma Intro incidence and nomenclature Update on Classification Diagnostic specimens Morphologic features Epithelioid Histology Biphasic Histology Immunohistochemical

More information

R. Julian Preston NHEERL U.S. Environmental Protection Agency Research Triangle Park North Carolina. Ninth Beebe Symposium December 1, 2010

R. Julian Preston NHEERL U.S. Environmental Protection Agency Research Triangle Park North Carolina. Ninth Beebe Symposium December 1, 2010 Low Dose Risk Estimation: The Changing Face of Radiation Risk Assessment? R. Julian Preston NHEERL U.S. Environmental Protection Agency Research Triangle Park North Carolina Ninth Beebe Symposium December

More information

Report series: General cancer information

Report series: General cancer information Fighting cancer with information Report series: General cancer information Eastern Cancer Registration and Information Centre ECRIC report series: General cancer information Cancer is a general term for

More information

PSA Screening for Prostate Cancer Information for Care Providers

PSA Screening for Prostate Cancer Information for Care Providers All men should know they are having a PSA test and be informed of the implications prior to testing. This booklet was created to help primary care providers offer men information about the risks and benefits

More information

CHAPTER 2. Neoplasms (C00-D49) March 2014. 2014 MVP Health Care, Inc.

CHAPTER 2. Neoplasms (C00-D49) March 2014. 2014 MVP Health Care, Inc. Neoplasms (C00-D49) March 2014 2014 MVP Health Care, Inc. CHAPTER SPECIFIC CATEGORY CODE BLOCKS C00-C14 Malignant neoplasms of lip, oral cavity and pharynx C15-C26 Malignant neoplasms of digestive organs

More information

WORKPLACE SAFETY AND INSURANCE APPEALS TRIBUNAL DECISION NO. 1557/14

WORKPLACE SAFETY AND INSURANCE APPEALS TRIBUNAL DECISION NO. 1557/14 WORKPLACE SAFETY AND INSURANCE APPEALS TRIBUNAL DECISION NO. 1557/14 BEFORE: M. Crystal: Vice-Chair HEARING: August 20, 2014 at Toronto Written DATE OF DECISION: December 4, 2014 NEUTRAL CITATION: 2014

More information

Update on Clinical Trials and Foundation Funded Grants

Update on Clinical Trials and Foundation Funded Grants Update on Clinical Trials and Foundation Funded Grants Mary Hesdorffer, MS, APRN-BC Medical Liaison Meso Foundation www.curemeso.org Delivering the Diagnosis Delivering the Diagnosis Day 1 Taking control

More information

Progress and Prospects in Ovarian Cancer Screening and Prevention

Progress and Prospects in Ovarian Cancer Screening and Prevention Progress and Prospects in Ovarian Cancer Screening and Prevention Rebecca Stone, MD MS Assistant Professor Kelly Gynecologic Oncology Service The Johns Hopkins Hospital 1 No Disclosures 4/12/2016 2 Ovarian

More information

The RNA strategy. RNA as a tool and target in human disease diagnosis and therapy.

The RNA strategy. RNA as a tool and target in human disease diagnosis and therapy. The RNA strategy RNA as a tool and target in human disease diagnosis and therapy. The Laboratory of RNA Biology and Biotechnology at the Centre for Integrative Biology (CIBIO) of the University of Trento,

More information

How many of you have checked out the web site on protein-dna interactions?

How many of you have checked out the web site on protein-dna interactions? How many of you have checked out the web site on protein-dna interactions? Example of an approximately 40,000 probe spotted oligo microarray with enlarged inset to show detail. Find and be ready to discuss

More information

Breast Cancer. Sometimes cells keep dividing and growing without normal controls, causing an abnormal growth called a tumor.

Breast Cancer. Sometimes cells keep dividing and growing without normal controls, causing an abnormal growth called a tumor. Breast Cancer Introduction Cancer of the breast is the most common form of cancer that affects women but is no longer the leading cause of cancer deaths. About 1 out of 8 women are diagnosed with breast

More information

Plaintiffs Experts Latest Pathological Theories

Plaintiffs Experts Latest Pathological Theories Plaintiffs Experts Latest Pathological Theories Kurt B. Gerstner Campbell Campbell Edwards & Conroy, P.C. One Constitution Center Boston, MA 02129 (617) 241-3086 kgerstner@campbell-trial-lawyers.com Kurt

More information

CancerStemCell Markers in Lung Cancers: Proofsof. Reservations. Lourdes Cortes-Dericks, PhD University of Hamburg Hamburg, Germany

CancerStemCell Markers in Lung Cancers: Proofsof. Reservations. Lourdes Cortes-Dericks, PhD University of Hamburg Hamburg, Germany CancerStemCell Markers in Lung Cancers: Proofsof ConceptsandSome Reservations Lourdes Cortes-Dericks, PhD University of Hamburg Hamburg, Germany Lung cancer: highest death rate and poorest patient survival

More information

Lung Cancer. This reference summary will help you better understand lung cancer and the treatment options that are available.

Lung Cancer. This reference summary will help you better understand lung cancer and the treatment options that are available. Lung Cancer Introduction Lung cancer is the number one cancer killer of men and women. Over 165,000 people die of lung cancer every year in the United States. Most cases of lung cancer are related to cigarette

More information

Future Directions in Cancer Research What does is mean for medical physicists and AAPM?

Future Directions in Cancer Research What does is mean for medical physicists and AAPM? Future Directions in Cancer Research What does is mean for medical physicists and AAPM? John D. Hazle, Ph.D., FAAPM, FACR President-elect American Association of Physicists in Medicine Professor and Chairman

More information

RENAL CANCER PATHOLOGY WHAT REALLY MATTERS? STEWART FLEMING UNIVERSITY OF DUNDEE

RENAL CANCER PATHOLOGY WHAT REALLY MATTERS? STEWART FLEMING UNIVERSITY OF DUNDEE RENAL CANCER PATHOLOGY WHAT REALLY MATTERS? STEWART FLEMING UNIVERSITY OF DUNDEE MAJOR PARADIGM SHIFT IN EARLY 1990S IN UNDERSTANDING RENAL CANCER Molecular differential pathology of renal cell tumours

More information

Genomic Medicine The Future of Cancer Care. Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America

Genomic Medicine The Future of Cancer Care. Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America Genomic Medicine The Future of Cancer Care Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America Personalized Medicine Personalized health care is a broad term for interventions

More information

Title: Immunohistochemical staining of radixin and moesin in prostatic adenocarcinoma

Title: Immunohistochemical staining of radixin and moesin in prostatic adenocarcinoma Author's response to reviews Title: Immunohistochemical staining of radixin and moesin in prostatic adenocarcinoma Authors: Tanner L Bartholow (bartholow.tanner@medstudent.pitt.edu) Uma R Chandran (chandranur@msx.upmc.edu)

More information

Test Information Sheet

Test Information Sheet Test Information Sheet GeneDx 207 Perry Parkway Gaithersburg, MD 20877 Phone: 888-729-1206 Fax: 301-710-6594 E-mail: wecare@genedx.com www.genedx.com/oncology OncoGene Dx: Breast/Ovarian Cancer Panel Sequence

More information

The Ontario Cancer Registry moves to the 21 st Century

The Ontario Cancer Registry moves to the 21 st Century The Ontario Cancer Registry moves to the 21 st Century Rebuilding the OCR Public Health Ontario Grand Rounds Oct. 14, 2014 Diane Nishri, MSc Mary Jane King, MPH, CTR Outline 1. What is the Ontario Cancer

More information

Surgeons Role in Symptom Management. A/Prof Cliff K. C. Choong Consultant Thoracic Surgeon Latrobe Regional Hospital GIPPSLAND

Surgeons Role in Symptom Management. A/Prof Cliff K. C. Choong Consultant Thoracic Surgeon Latrobe Regional Hospital GIPPSLAND Surgeons Role in Symptom Management A/Prof Cliff K. C. Choong Consultant Thoracic Surgeon Latrobe Regional Hospital GIPPSLAND Conditions PLEURAL Pleural effusion Pneumothorax ENDOBRONCHIAL Haemoptysis

More information

MesoPDT. Photodynamic Therapy for malignant pleural mesothelioma ONCO-THAI. Image Assisted Laser Therapy for Oncology

MesoPDT. Photodynamic Therapy for malignant pleural mesothelioma ONCO-THAI. Image Assisted Laser Therapy for Oncology MesoPDT Photodynamic Therapy for malignant pleural mesothelioma ONCO-THAI Image Assisted Laser Therapy for Oncology Unité Inserm ONCO-THAI «Image Assisted Laser Therapy for Oncology» Inserm ONCO-THAI "Image

More information

Rotation Specific Goals & Objectives: University Health Network-Princess Margaret Hospital/ Sunnybrook Breast/Melanoma

Rotation Specific Goals & Objectives: University Health Network-Princess Margaret Hospital/ Sunnybrook Breast/Melanoma Rotation Specific Goals & Objectives: University Health Network-Princess Margaret Hospital/ Sunnybrook Breast/Melanoma Medical Expert: Breast Rotation Specific Competencies/Objectives 1.0 Medical History

More information

Asbestos Health Risks. Dr Andrew Pengilley Acting Chief Health Officer

Asbestos Health Risks. Dr Andrew Pengilley Acting Chief Health Officer Asbestos Health Risks Dr Andrew Pengilley Acting Chief Health Officer Asbestos Asbestos is a name given to several different fibrous minerals Three main commercial types are Chrysotile (white asbestos)

More information

Appendix 2 Molecular Biology Core Curriculum. Websites and Other Resources

Appendix 2 Molecular Biology Core Curriculum. Websites and Other Resources Appendix 2 Molecular Biology Core Curriculum Websites and Other Resources Chapter 1 - The Molecular Basis of Cancer 1. Inside Cancer http://www.insidecancer.org/ From the Dolan DNA Learning Center Cold

More information

Summary of treatment benefits

Summary of treatment benefits Risk Management Plan PEMETREXED Powder for concentrate for Solution for infusion Pemetrexed is also indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non small cell

More information

International Journal of Case Reports in Medicine

International Journal of Case Reports in Medicine International Journal of Case Reports in Medicine Vol. 2013 (2013), Article ID 409830, 15 minipages. DOI:10.5171/2013.409830 www.ibimapublishing.com Copyright 2013 Andrew Thomas Low, Iain Smith and Simon

More information

CONTRACTING ORGANIZATION: University of Alabama at Birmingham Birmingham, AL 35294

CONTRACTING ORGANIZATION: University of Alabama at Birmingham Birmingham, AL 35294 AD Award Number: W81XWH-08-1-0030 TITLE: Regulation of Prostate Cancer Bone Metastasis by DKK1 PRINCIPAL INVESTIGATOR: Gregory A. Clines, M.D., Ph.D. CONTRACTING ORGANIZATION: University of Alabama at

More information

A 43 year old male presents with abdominal complaints. An axial CT reveals.

A 43 year old male presents with abdominal complaints. An axial CT reveals. A 43 year old male presents with abdominal complaints. An axial CT reveals. Diagnosis: Gastrointestinal Stromal Tumor Location: stomach Size: 12 cm Mitotic count: 10 mitoses / 50 high power fields Risk

More information

Focusing on results not data comprehensive data analysis for targeted next generation sequencing

Focusing on results not data comprehensive data analysis for targeted next generation sequencing Focusing on results not data comprehensive data analysis for targeted next generation sequencing Daniel Swan, Jolyon Holdstock, Angela Matchan, Richard Stark, John Shovelton, Duarte Mohla and Simon Hughes

More information

Genomic Analysis of Mature B-cell Malignancies

Genomic Analysis of Mature B-cell Malignancies Genomic Analysis of Mature B-cell Malignancies Update and Lessons Learned Omar Abdel-Wahab, MD Memorial Sloan Kettering Cancer Center Human Oncology and Pathogenesis Program and Leukemia Service Disclaimer:

More information

Investigating Community Cancer Concerns--Deer Park Community Advisory Council, 2008

Investigating Community Cancer Concerns--Deer Park Community Advisory Council, 2008 Investigating Community Cancer Concerns--Deer Park Community Advisory Council, 2008 David R. Risser, M.P.H., Ph.D. David.Risser@dshs.state.tx.us Epidemiologist Cancer Epidemiology and Surveillance Branch

More information

Rare Thoracic Tumours

Rare Thoracic Tumours Rare Thoracic Tumours 1. Epithelial Tumour of Trachea 1 1.1 General Results Table 1. Epithelial Tumours of Trachea: Incidence, Trends, Survival Flemish Region 2001-2010 Both Sexes Incidence Trend EAPC

More information

Robert Bristow MD PhD FRCPC

Robert Bristow MD PhD FRCPC Robert Bristow MD PhD FRCPC Clinician-Scientist and Professor, Radiation Oncology and Medical Biophysics, University of Toronto and Ontario Cancer Institute/ (UHN) Head, PMH-CFCRI Prostate Cancer Research

More information

Small Cell Lung Cancer

Small Cell Lung Cancer Small Cell Lung Cancer Types of Lung Cancer Non-small cell carcinoma (NSCC) (87%) Adenocarcinoma (38%) Squamous cell (20%) Large cell (5%) Small cell carcinoma (13%) Small cell lung cancer is virtually

More information