KREATECH DIAGNOSTICS LUNG CANCER PROBES

Transcription

1 KREATECH DIAGNOSTICS LUNG CANCER PROBES REPEAT-FREE POSEIDON FISH PROBES FOR DIAGNOSIS IN LUNG CANCER

2 molecular PROFILING OF LUNG CANCER Lung Cancer remains the leading cause of cancer related deaths worldwide. Annually about 1.6 million new cases are diagnosed and prognoses are poor. Genetic Aberrations In non-small cell lung cancer Lung tumors can be divided into two main subtypes based on histological appearance: non-small cell lung cancer (NSCLC, ± 80%) and small cell lung cancer (SCLC, ± 20%). NSCLC can be divided in Adenocarcinoma (± 60% of NSCLC). Large Cell Carcinoma (± 20% of NSCLC). Squamous Cell Carcinoma (SCC) (± 20% of NSCLC). AKT1, 1% PTEN, 4% PIK3CA,1% NRAS, 1% BRAF, 2% MEK1, 1% DDR2, 4% To be characterized, 41% HER2, 3% KRAS, 15% ALK, 5% ROS1, 2% MET, 2% RET, 1% FGFR1, 4% EGFR1, 13% Over the past decade, it has become evident that subsets of NSCLC can be further defined at the molecular level by recurrent 'driver' aberrations in multiple oncogenes, including EGFR, KRAS, ALK, MET, RET, ROS1, and FGFR1 (see figure to the right). Frequency of genetic aberrations found in non-small cell lung cancer (NSCLC). Mutations are shown in purple, blue and green and amplifications and rearrangements in shades of orange. Source: Mycancergenome.org Possible testing algorithm for non-small cell lung cancer specimens Squamous Cell (20%) Non-Small Cell (80%) Adenocarcinoma (60%) LUNG CANCER Specimen (100%) EGFR Activatingting Mutation Small Cell (20%) Therapy Decisions No further diagnosis Therapy Decisions Novel therapies and treatment strategies are emerging. With the approval of novel cancer drugs like crizotinib (XALKORI ) and the establishment and continuous development of testing strategies as depicted in the figure to the left, there is a growing demand for (molecular) diagnostic tests for NSCLC. KREATECH has developed a range of REPEAT-FREE POSEIDON FISH probes that are optimized for the use on non-small cell lung cancer tissue. You can find information on these probes in this brochure. For additional information on these probes or any of our other products you can also visit or scan the QR code below. FGFR1 Amplifi cation Compounds in Clinical Trials EGFR Negative or nonactivating RET Break ALK Break (refl ux test) Compounds in Clinical Trials ROS1 Break (refl ux test) Eligible for crizotinib (XALKORI ) treatment MET Amp. (refl ux test) Adapted from Serracino et. al., Surgical Pathology 12 (2012);

3 ALK GENE REARRANGEmENTS IN NON-SmALL CELL LUNG CANCER ALK FACTS [Ŧ] ALK (anaplastic lymphoma kinase) gene rearrangements are observed in 3 7% of NSCLC cases. The majority ALK rearrangements found in NSCLC are fusions of 5 of portions of the echinoderm microtubuleassociated protein-like 4 (EML4) gene with 3 portions of the ALK gene. At least nine different EML4-ALK fusion variants have been identified in NSCLC. In the vast majority of cases, ALK rearrangements are non-overlapping with other oncogenic mutations found in NSCLC (e.g. EGFR mutations, KRAS mutations, etc.). EML4-ALK fusions are associated with EGFR tyrosine kinase inhibitor (TKI) resistance. Promising results have been obtained with specific ALK inhibitors such as crizotinib. FDA approved crizotinib in August In October 2012 it was approved in the European Union. REPEAT-FREE POSEIDON ALK FISH PROBES ALK (2p23) Break. Cat. # KBI Dual color break assay. Captures all ALK rearrangements. Distal (3 ) ALK (2p23) region probe is direct-labeled with PlatinumBright 550 (red). Proximal (5 ) ALK (2p23) region probe is directlabeled with PlatinumBright 495 (green). ALK/EmL4 t(2;2); inv(2) Fusion. Cat. # KBI Dual color fusion assay. Detection of ALK-EML4 Fusion. Detects fusion of ALK and EML4 gene regions by paracentric inversion. Distal (3 ) ALK(2p23) region probe is direct-labeled with PlatinumBright 550 (red). Distal (5 ) EML4 (2p21) region probe is directlabeled with PlatinumBright 495 (green). D2S392 D2S392 2p KB 2p KB SHGC SHGC D2S405 ALK RH KB ALK Gap: 12 MB ALK (2p23) Break probe hybridized to NSCLC tissue showing translocation involving the ALK region at 2p23 (1RG1R1G). 2p21 SHGC SHGC EML4 350 KB ALK/EML4 t(2;2); inv(2) Fusion probe hybridized to NSCLC tissue showing ALK-EML4 fusion (2RG1R1G). 2 2 Normal Cell ALK (2p23) translocation Normal Cell EML4-ALK Fusion [Ŧ] For references, please see page 7 3

4 ROS1 GENE REARRANGEmENTS IN NON-SmALL CELL LUNG CANCER ROS1 FACTS [Ŧ] ROS1 (c-ros oncogene 1, receptor tyrosine kinase) gene rearrangements represent 1-2% of aberrations in NSCLC. ROS1 gene rearrangements define a unique molecular subset of NSCLC. These are mainly non-overlapping with other oncogenic aberrations (e.g. EGFR mutations, KRAS mutations, ALK rearrangements, etc.). Different ROS1 rearrangements have been described in NSCLC including SLC34A2-ROS1, CD74-ROS1, EZR-ROS1, TPM3- ROS1, SDC4-ROS1 and GOPC-ROS1. The GOPC-ROS1 fusion is characterized by deletion of a 240 kb DNA fragment on chromosome 6q distal of ROS1 exon 42 and has been identified in NSCLC. Case studies describe patients with advanced NSCLC harboring ROS1 rearrangements with partial responses to crizotinib (XALKORI ) treatment. REPEAT-FREE POSEIDON ROS1 FISH PROBE ROS1 (6q22) Break. CAT# KBI Captures all ROS1 rearrangements. Detection of GOPC-ROS1 fusion by deletion. Distal (5 ) ROS1 (6q22) region probe is direct-labeled with PlatinumBright 550 (red). Proximal (3 ) ROS1 (6q22) region probe is direct-labeled with PlatinumBright 495 (green). SHGC KB 6 RH69070 ROS1 RH q22 RH68126 GOPC Exon 42 Exon KB Hybridization of ROS1 (6q22) Break Probe (KBI-10752) to a tissue section harboring a ROS1 rearrangement. Hybridization of ROS1 (6q22) Break Probe (KBI-10752) to a Cell Line harboring a GOPC-ROS1 rearrangement (deletion of red signal). Scan the QR code below for more information on the ROS1 (6q22) Break probe design. Normal Cell ROS1 (6q22) translocation GOPC-ROS1 fusion, fusion to gene regions distal to GOPC, or deletion of the 6q arm distal of exon 42 sh-probes/solid-tumors/ros1-6q22-break.html [Ŧ] For references, please see page 7 4

5 met AmPLIFICATION AND RET REARRANGEmENTS IN NON-SmALL CELL LUNG CANCER met FACTS [Ŧ] In NSCLC, multiple mechanisms of MET activation have been reported, including gene amplification and mutation. MET amplification is found in 2-4% in previously untreated NSCLC patients. Patients harboring activating EGFR mutations can acquire resistance to EGFR TKI therapy. MET amplification is found in 5-20% of these cases. A case has been reported of a NSCLC patient with a MET amplification that responded to crizotinib. RET FACTS [Ŧ] RET gene rearrangement represents 1-2% of aberrations in NSCLC, and can include KIF5B-RET or CCDC6-RET fusions. RET gene rearrangements define a unique molecular subset of NSCLC. These are mainly non-overlapping with other oncogenic aberrations (e.g. ALK- and ROS1 rearrangements, etc.). Recent clinical studies showed inhibition of RET with multiple kinase inhibitors in RET overexpressing cells. Evaluation of RET gene rearrangements could be applicable in clinical practice to detect NSCLC patients that may respond to RET inhibitors like vandetanib, sunitinib or sorafenib. REPEAT-FREE POSEIDON met AND RET FISH PROBES met (7q31) / SE 7 Amplifi cation. CAT# KBI Dual color assay to detect amplification of the MET (7q31) gene region. MET (7q31) gene region probe direct-labeled with PlatinumBright 550 (red). Control region probe SE 7 (D7Z1) direct-labeled PlatinumBright 495 (green). RET (10q11) Break. CAT # KBI Captures all RET rearrangements, including KIF5B- RET Fusion. Proximal (5 ) RET (10q11) region probe is directlabeled with PlatinumBright 550 (red). Distal RET (3 ) (10q11) region probe is directlabeled with PlatinumBright 495 (green). RH D7S q11 GDB: RET D10S KB C-MET 420 K SHGC KB 7q31 RH Hybridization of MET Amplification Probe (KBI-10719) to a tissue section showing MET amplification. 10 Hybridization of RET (10q11) Break Probe (KBI-10753) to a tissue section harboring a RET rearrangement. 7 Normal Cell MET (7q31) amplification Normal Cell RET (10q11) translocation [Ŧ] For references, please see page 7 5

6 FGFR1 GENE AmPLIFICATION IN NON-SmALL CELL LUNG CANCER FGFR1 FACTS [Ŧ] Amplification of the fibroblast growth factor receptor type 1 gene (FGFR1) has been observed in numerous cancer types including Squamous Cell Carcinoma (SCC) of the lung. FGFR1 amplifications represent ±4% of aberrations found in NSCLC and represent around 17% of aberrations in SCC of the lung. With the development of new therapeutic strategies, FGFR1 amplification could act as a valuable biomarker for R&D and provide an attractive tool for clinical stratification. REPEAT-FREE POSEIDON FGFR1 FISH PROBE FGFR1 (8p11) / SE 8 Amplifi cation. CAT# KBI Dual color assay to detect amplification of the FGFR1 (8p11) gene region. The REPEAT-FREE POSEIDON FGFR1 (8p11) has been validated on a cohort of 100 NSCLC samples [1]. FGFR1 (8p11) gene region probe direct-labeled with PlatinumBright 550 (red). Control region probe SE 8 (D8Z1) direct-labeled with PlatinumBright 495 (green). RH p11 A B FGFR1 540KB D8S414 8 C D FGFR1 (8p11)/ SE 8 probe hybridized to SCC NSCLC tissue (A). Normal cell pattern ( B), amplification of FGFR1 (C) and polysomy (D). Images kindly provided by Dr. Marcus Otte, ORIDIS Biomarkerrs, Vienna, Austria. [1] Presented at the ADAPT meeting 2012, Washington, DC: Scan the QR code below for more information. Normal Cell FGFR1 (8p11) amplification [Ŧ] For references, please see page 7 Documenten/PDF/005966_Kreatech_poster_lr3.pdf 6

7 REPEAT-FREE POSEIDON DNA FISH PROBES FOR LUNG CANCER Product information DESCRIPTION COLOR CONTENT CAT.# ON ALK (2p23) Break Red/Green 10 Tests KBI ON ALK/EML4 t(2;2); inv(2) Fusion Red/Green 10 Tests KBI ON ROS1 (6q22) Break Red/Green 10 Tests KBI ON C-MET (7q31) / SE 7 Red/Green 10 Tests KBI ON RET (10q11) Break Red/Green 10 Tests KBI ON FGFR1 (8p11) / SE 8 (D8Z1) Red/Green 20 Tests KBI ON FGFR1 (8p11) / SE 8 (D8Z1) Red/Green 50 Tests KBI Other relevant Lung Cancer Probes ON EGFR, Her-1 (7p11) / SE7 Red/Green 10 Tests KBI ON htert (5p15) / 5q31- for Tissue Red/Green 10 Tests KBI ON ERCC1 (19q13) & ZNF443 (19p13) Red/Green 10 Tests KBI FGFR2 amplification probe Red/Green Inquire Inquire FGFR4 amplification probe Red/Green Inquire Inquire For more information on our products for Lung Cancer Specimens, please contact your local sales representative or contact us via customerservice@kreatech.com For technical inquiries, please contact techservices@kreatech.com If you are looking for a FISH probe that you can t find in our catalogue or on our website, you can contact us at FISH4U@kreatech.com to inquire about a custom made probe Selected Literature References ALK References Koivunen et al. Clin Cancer Res. 2008;14: Kwak et al. N Engl J Med. 2010;363: Shinmura et al. Lung Cancer. 2008:61: Soda et al. Nature. 2007; 448: Takeuchi et al. Clin Cancer Res. 2008; 14: Wong et al. Cancer. 2009;115: Choi et al. Cancer Res. 2008; 68: Horn and Pao, J Clin Oncol. 2009;27: Inamura et al. Mod Pathol. 2009;22: Shaw et al. J Clin Oncol. 2009;27: ClinicalTrials.gov NCT ClinicalTrials.gov NCT Wu, S.G. et al. J Thorac Oncol. 2012: 7: ROS1 References Bergethon, K et al., J Clin Oncol 2012; 30: Davies, K.D. et al., Clin Cancer Res 2012; 18; Takeuchi, K. et al., Nature Medicine 2012: 18: Rikova et al., Cell, 2007, 131: Rimkunas et al.,clin. Can. Res., 2012, 18: Suehara, Y. et al., Clin Cancer Res Shaw, A. et al., J.Clin Oncol 30, 2012 (suppl; abstr 7508). MET References Bean et al. Proc Natl Acad Sci U S A. 2007,104: Cappuzzo et al. Ann Oncol. 2009;20: Chen et al. Pathol Oncol Res. 2009;15: Engelman, J.M. et al, Science 2007:18;316: Kubo et al. Int J Cancer. 2009;124: Okuda et al. Cancer Sci. 2008;99: Onozato et al. J Thorac Oncol. 2009;4:5-11. Kong-Beltran et al. Cancer Res. 2006;66: RET References Takeuchi, K. et al., Nature Medicine 2012: 18: Suehara, Y. et al., Clin Cancer Res Lipson. D. et al. Nature Medicine 2012; 18: Kohno, T. et al., Nat Med 2012: 18: Sasaki, H. et al., Cancer Medicine 2012: 1: Wang, R. et al., J. Clin Oncol FGFR1 References Weiss et. al., Sci Transl Med Dec 15;2(62):62ra93. Schildhaus et. al., Mod Pathol Nov;25(11): Dutt et. Al.,PLoS One. 2011;6:e doi: /journal. pone

8 Ordering information How to place an order Orders are accepted by phone, fax, or mail. When placing an order please include the following information: Your account number (required) Your name and phone number Complete billing address Complete shipping address Purchase order number Catalogue number and description of product Quantity needed VAT number (where applicable) Please visit our website for information regarding our terms and conditions If it is necessary to send a written order confirmation by mail or fax, please indicate clearly that your order is marked "CONFIRMATION". This will assist in avoiding shipment duplications. KREATECH cannot be held responsible in cases where the latter procedure is not followed. We accept Visa and Mastercard If you wish to pay with a credit card please use the fax or option to send your order and please provide the name of your credit card, account number, expiration date and security code when placing credit card orders. International KREATECH Diagnostics Vlierweg LG Amsterdam The Netherlands Phone: + 31 (0) Fax: +31 (0) Benelux KREATECH Diagnostics Vlierweg LG Amsterdam The Netherlands Phone: + 31 (0) Fax: +31 (0) France KREATECH Diagnostics 20 Avenue de la Paix Strasbourg Cedex Phone: + 33 (0) Fax: +33 (0) Germany KREATECH Diagnostics Vlierweg LG Amsterdam The Netherlands Phone: + 49 (0) Fax: + 31 (0) United Kingdom KREATECH Diagnostic 52 New Town, Uckfield East Sussex, TN22 5DE Phone: +44 (0) Fax: +44 (0) Disclaimer Marketing Materials: The content of this brochure is explicitly not meant for the North American region. If you are a resident in this region please contact the North American sales office to obtain the appropriate product information for your country of residence. For more information please visit our website: KREATECH Diagnostics Published 25 February 2013