Pancreatic Cancer. Hereditary Pancreatic Cancer A Guide for Clinicians KNOWING WHAT TO LOOK FOR KNOWING WHERE TO LOOK AND KNOWING WHAT IT MEANS

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1 Pancreatic Cancer Hereditary Pancreatic Cancer A Guide for Clinicians KNOWING WHAT TO LOOK FOR KNOWING WHERE TO LOOK AND KNOWING WHAT IT MEANS

2 Hereditary Pancreatic Cancer Panel Advances in molecular genetics have led to the identification of numerous genes associated with inherited susceptibility to pancreatic cancer (adenocarcinoma). While the majority of pancreatic cancer is not inherited, up to 10% of all cases of pancreatic cancer are associated with a cancer predisposition gene 1,2,3. Determining which genes to test and the order in which to test them can be complex, expensive and time consuming. Identifying patients at increased risk of developing pancreatic cancer due to a hereditary cancer syndrome can allow for early detection or prevention of cancer. The Pancreatic Cancer Panel offered at GeneDx is a comprehensive panel that utilizes next generation sequencing and exon-level microarray to test for mutations in 16 genes associated with increased risk for developing pancreatic cancer. Genes Included in the Pancreatic Cancer Panel The 16 genes included in the Pancreatic Cancer Panel can be categorized into three main groups: High Risk, Moderate Risk, and Newly-Identified Risk as described in Table 1. High Risk Moderate Risk Newly-Identified Risk CDKN2A, STK11,VHL Well studied Lifetime risk of developing pancreatic cancer: 10% Can increase risk for other cancers APC, BRCA1, BRCA2, MLH1, MSH2, MSH6, PALB2, PMS2, EPCAM Well studied Lifetime risk of developing pancreatic cancer: 2-10% Can increase risk for other cancers ATM, TP53, CDK4, XRCC2 Not as well studied with regard to pancreatic cancer, data based on a small number of patients or patients within a specific ethnicity Precise lifetime risks of pancreatic cancer not yet determined Can increase risk for other cancers Table 1: Composition of Pancreatic Cancer Panel 1

3 Lifetime Cancer Risks High Risk Genes The Pancreatic Cancer Panel includes highly penetrant genes that are associated with well-defined cancer syndromes with increased risk for pancreatic cancer as well as other cancers. These include: CDKN2A-Familial atypical multiple mole/melanoma syndrome (FAMMM) FAMMM is characterized by multiple melanocytic nevi (typically defined as greater than 50), atypical melanocytic nevi, and an increased risk of developing melanoma (28-76%) and pancreatic cancer (17%). Sarcoma, breast cancer, and lung cancer have also been reported with CDKN2A mutations. STK11-Peutz-Jeghers syndrome (PJS) PJS is characterized by the combination of gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. The risk of cancer in PJS is significant and multiple organ systems are at risk. Overall, individuals with PJS have anywhere from an 85-93% chance of developing cancer in their lifetime, and, more specifically, the risk of pancreatic cancer in individuals with PJS is estimated to be between 11-36%. VHL-von Hippel Lindau disease (VHL) VHL disease is characterized by the development of benign and malignant tumors. The characteristic lesions in individuals with VHL are typically found within the spinal cord, and rarely in the peripheral nerves. Retinal hemangioblastomas are also common. Pheochromocytomas, in one or both adrenal glands, may cause hypertension (sustained or episodic) and are usually benign, although rare malignant pheochromocytomas have been reported 4. Individuals with VHL have up to a 70% risk for clear cell renal carcinoma by age 60, and a 5-17% risk for pancreatic neuroendocrine tumors. Moderate Risk and Newly-Identified Risk Genes In addition to the high risk genes, this panel includes genes that impart a CLINICIAN GUIDE FOR HEREDITARY PANCREATIC CANCER 2

4 moderate risk for pancreatic cancer and for which consensus guidelines for pancreatic cancer screening and prevention are not available. Recommendations are generally based on expert opinion. These genes include: APC, BRCA1, BRCA2, MLH1, MSH2, MSH6, PALB2, PMS2, and EPCAM (Table 2). Finally, four genes included in the panel have been identified in families with apparent hereditary pancreatic cancer, but precise lifetime cancer risks for these genes have not been determined and/or need confirmation. They include: ATM, TP53, CDK4, and XRCC2 (Table 2). Genes Associated Cancers and Risks High Risk Moderate Risk CDKN2A Pancreatic (17%), Melanoma (28-76%) 5,6 STK11 VHL APC BRCA1 BRCA2 MLH1 MSH2 MSH6* PMS2* EPCAM* Pancreatic (11-36%), Female Breast (32-54%), Colorectal (39%), Gastric (30%), Ovarian tumors (21%), Lung (15%), Small intestine (13%), Cervical (10%), Endometrial (10%), Testicular tumors (9%) 7,8 Pancreatic neuroendocrine tumors (5-17%), Clear cell renal cell carcinoma (up to 70%), other characteristic tumors include hemangioblastomas and pheochromocytomas 9,10 Colorectal (up to 93%), Duodenal or periampullary (5%), Gastric, Thyroid, Pancreatic, Brain, Liver 11 Female Breast (57-87%), Ovarian (24-54%), Prostate, Pancreatic, Male Breast, Fallopian tube, Primary peritoneal, Endometrial (serous) 12,13,14,15,16,17, 18,19,20,21,22,23 Pancreatic (5-7%), Female Breast (41-84%), Prostate (20-34%), Ovarian (11-27%), Male Breast (4-7%), Melanoma, Fallopian tube, Primary peritoneal, Endometrial (serous) 12,15,16,21,22,23,24,25,26,27 Colorectal (15-80%), Endometrial (15-61%), Ovarian (1-24%), Gastric, Pancreatic, Biliary tract, Urothelium, Small bowel, Brain, Sebaceous neoplasms 28,29,30,31,32,33,34,35,36 PALB2 Female Breast, Male Breast, Pancreatic, Ovarian 37,38,39,40 Newly-Identified Risk ATM Female Breast, Colon, Pancreatic 41,42,43 TP53 Female Breast, Soft tissue sarcoma, Osteosarcoma, Brain, Hematologic malignancies, Adrenocortical carcinoma Overall risk for cancer: nearly 100% in females, 73% in males 44,45,46,47 CDK4 Melanoma (74%), Pancreatic, Non-melanoma skin cancer 48,49 XRCC2 Female Breast, Pancreatic 50,51,52 Table 2: Cancers and Lifetime Risks Associated with Genes in the Pancreatic Cancer Panel *Tumor spectrum is representative of Lynch syndrome; data are limited with regard to the association of certain cancers with mutations in MSH6, PMS2 and EPCAM. 3

5 Inheritance of the Genes in the Pancreatic Cancer Panel The genes in the Pancreatic Cancer Panel are inherited in an autosomal dominant manner. Therefore, an individual carrying a disease-causing mutation in any of the genes above has a 50% chance of transmitting the mutation to a child, either male or female. Most individuals with a mutation in one of the genes on the panel inherited it from a parent, and therefore the siblings of an individual with a mutation carry a 50% chance to have the same disease-causing mutation. The risk for other family members to carry the same mutation depends on which side of the family transmits the mutation, and how closely related the family member is to your patient. While each of the genes on the panel is associated with an increased risk for pancreatic cancer when a single mutation in the gene is present, some of the genes on the panel are also associated with rare autosomal recessive syndromes if an individual has a mutation in both copies of the gene (biallelic mutations). The genes known to be associated with recessively inherited syndromes are listed in Table 3. If both a mother and father are carriers for a mutation within the same gene*, each of their children has a 25% chance to inherit both mutations, resulting in the recessive syndrome associated with that particular gene. If your patient tests positive for one of these mutations and wishes to have children in the future, then careful review of his or her partner s family history and possible genetic testing of the partner are needed to assess the reproductive risks associated with mutations in these genes. Gene MLH1, MSH2, MSH6, PMS2, EPCAM BRCA2, PALB2, XRCC2 ATM Autosomal Recessive Disorders Constitutional mismatch repair deficiency syndrome * there is one case report of a child with this condition that has one mutation in EPCAM and one mutation in MSH2 Fanconi anemia Ataxia-telangiectasia Table 3: Genes Associated with Autosomal Recessive Disorders CLINICIAN GUIDE FOR HEREDITARY PANCREATIC CANCER 4

6 Clinical Indications for the Pancreatic Cancer Panel The Pancreatic Cancer Panel is appropriate for individuals whose personal and/or family history is suggestive of a hereditary predisposition to pancreatic cancer. This includes: Individuals with a family history of pancreatic cancer in multiple close relatives or a relative with early-onset pancreatic cancer ( 50) Individuals diagnosed with pancreatic cancer at age 50 Individuals with multiple related primary cancers, including pancreatic cancer Individuals with several relatives affected with related cancers spanning multiple generations Genetic Test Results and What They Mean There are three possible outcomes of genetic testing: positive, negative, and variant of unknown significance (VUS). Positive Result A positive result indicates that a disease-causing mutation was identified in that individual and the risk for cancer is increased. A positive result provides valuable information to the patient and physician, as well as family members, and can assist in making management and treatment decisions. Furthermore, testing of the patient s family members can allow for accurate predictions of cancer risks. Negative Result A negative result means that a disease-causing mutation was not identified in the individual tested. A negative result can have different interpretations based on the following scenarios: True Negative Result: An individual who tests negative for a known familial mutation in a cancer-predisposing gene that has been positively identified in another family member. The risk for cancer in this individual is generally 5

7 not expected to be greater than the general population. In some cases, this interpretation may be limited by the identification of a mutation in a gene with modest cancer risk or a mutation in a gene that has been recently described (i.e., newly-identified risk genes previously described) with cancer risk and for which there are currently limited data to predict cancer risk. In these situations, not all of the cancer in the family may be attributed to the identified familial gene mutation. Therefore, clinical assessment of the complete family history of cancer and personal risk factors is important to determine appropriate management. Uninformative Negative Result: If testing was performed on an individual with a cancer diagnosis, this means that we do not have an explanation for why this individual developed cancer. Genetic counseling is recommended, as additional testing may be considered based on the individual s medical and family history. If testing was performed on an individual without a personal history of cancer and based only on family history, the risk for cancer may remain increased, as the exact cause of the cancer in the family remains unknown. Testing of an affected family member may help clarify this individual s cancer risks. Variant of Unknown Significance (VUS) A variant of unknown significance (VUS) indicates that a genetic variant was identified in a cancer predisposing gene but the pathogenicity of the variant cannot be clearly established. To further clarify the clinical significance of this variant, testing of family members may be helpful. If a relative with a related cancer is found to have the same variant, it may provide evidence that the variant may be disease-causing. The greater the number of affected family members who carry the VUS, the greater is the likelihood that the VUS is pathogenic. With consistent linkage of the VUS with family members with related cancers, in addition to other evidence, the variant found may be reclassified as a family-specific mutation and predictive genetic testing can be offered to extended family members. Conversely, a VUS could be determined to be benign through this and other research. GeneDx will review a patient s detailed family history to determine if family members are eligible for complementary targeted variant testing through our Variant Testing Program. CLINICIAN GUIDE FOR HEREDITARY PANCREATIC CANCER 6

8 Genetic Counseling Pre-test counseling is recommended for individuals who are considering genetic testing and are either interested in understanding their risks and/ or meet the clinical criteria for testing. If a disease-causing mutation has already been identified in a family member, testing of the specific mutation is appropriate. If a disease-causing mutation has never been identified, an affected family member with the highest likelihood for a positive result (e.g., early onset disease or multiple primaries) is the preferred person for initial testing within a family. If an affected family member is not available for testing, an unaffected family member can be tested, although a negative test result will not guarantee that the individual does not have an increased cancer risk. Once patients make the decision to undergo testing, post-test genetic counseling is recommended to understand the implications of the results. Genetic counseling services across the country can be found at: Management Currently, endoscopic ultrasound and/or magnetic resonance imaging are considered the most accurate tools for surveillance for pancreatic cancer. The use of these surveillance methods and other management strategies vary depending on the specific disease-causing mutation identified on the Pancreatic Cancer Panel and may vary based on the institution and/or availability of such technologies. Management guidelines for a number of the genes within the pancreatic cancer panel are discussed in Table 4. 28,53,54,55,56 These guidelines are current as of For many of the syndromes found within the Pancreatic Cancer Panel, you may visit for the most up-to-date recommendations, including ages to begin surveillance and current screening frequencies. For VHL, surveillance begins in early childhood; a consultation with a healthcare provider with expertise in VHL is recommended to review ages to begin surveillance and screening frequencies. 7

9 Gene BRCA1/ BRCA2 CDKN2A PALB2 STK11 VHL Management Guidelines Increased breast awareness including self breast exams Routine clinical breast exams Annual breast MRI and mammography starting at an early age Consider transvaginal ultrasound of ovaries and CA-125 blood tests Consider full body skin examination Consider pancreatic cancer screening Consider routine prostate cancer screening starting at an early age Consider the use of risk-reducing medications (such as tamoxifen, raloxifene and oral contraceptives) Consider prophylactic mastectomy Salpingo-oopherectomy is recommended (as early as the 30s-40s) once a woman has completed childbearing Routine total body dermatological exams starting at an early age Routine skin self-exams Consider pancreatic cancer screening (e.g. magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound, etc.) either clinically or through clinical research programs Consider pancreatic cancer screening (e.g. magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound, etc.) either clinically or through clinical research programs Consider a high risk breast cancer surveillance protocol (e.g. consider the addition of breast MRIs to routine mammography) Frequent colonoscopy starting at an early age Routine upper endoscopy starting at an early age Routine pancreatic cancer screening (e.g. magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound, etc.) starting at an early age Routine small bowel visualization starting at an early age Routine pelvic exams with consideration of transvaginal ultrasound Increased breast awareness including self breast exams Routine clinical breast exams Annual breast MRI and mammography starting at an early age Annual physical exams Routine blood pressure monitoring Routine MRI of brain/spine Routine ophthalmology exams Routine formal hearing evaluations Routine urine/blood fractionated metanephrines to screen for pheochromocytoma Routine imaging (e.g. abdominal ultrasounds, MRIs) to evaluate the kidneys, adrenal glands, and pancreas Pregnant women affected with VHL require additional monitoring Table 4: Management Guidelines for Mutation Carriers CLINICIAN GUIDE FOR HEREDITARY PANCREATIC CANCER 8

10 Resources for Patients: American Cancer Society: National Cancer Institute: Pancreatic Cancer Action Network: Pancreatic Cancer Alliance: National Pancreas Foundation: GeneDx: National Society of Genetic Counselors: References 1. Lynch HT, Smyrk, Kern SE, et al. Familial pancreatic cancer: a review. Semin Oncol 23:251, Brand RE, Lynch HT. Hereditary pancreatic adenocarcinoma. A clinical perspective. Med Clin North Am 84:665, Grover S, Syngal S. Hereditary pancreatic cancer. Gastroenterol 139:1076, Jimenez C et al. Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-Lindau disease: targeting angiogenic factors in pheochromocytoma and other von Hippel-Lindau disease-related tumors. J Clin Endocrinol Metab. Feb;94(2):386-91, Vasen HF, Gruis NA, Frants RR, et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-leiden). Int J Cancer 87(6):809, Bishop DT, Demenais F, Goldstein AM, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst 94:894, Hearle N, Schumacher V, Menko FH, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12(10):3209, Giardiello FM et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. Dec;119(6): , Maher ER, Neumann HP, and Richard S. von Hippel-Lindau disease: a clinical and scientific review. Eur J Hum Genet. Jun;19(6):617-23, Lonser RR et al. von Hippel-Lindau disease. Lancet. Jun;361(9374): , Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. June; 138(6): , Antoniou A et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. May;72(5): , Chen S and Parmigiani G. Meta-anlaysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. Apr;25(11): , King MC et al. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. Oct;302(5645):643-6, Risch HA et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario. J Natl Cncer Inst. Dec;98(23): , Levine DA et al. Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations. J Clin Oncol. Nov;21(22):4222-7, Claus EB et al. The genetic attributable risk of breast and ovarian cancer. Cancer Jun 1;77(11): Pennington KP et al. BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. Cancer Jan;119(2): Brose MS et al. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst Sep;94(18): Leongamornlert D et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer May 8;106(10): Liede A et al. Cancer Risks for Male Carriers of Germline Mutations in BRCA1 or BRCA2: A Review of the Literature. J Clin Oncol Feb 15;22(4): Thompson D, Easton DF, and the Breast Cancer Linkage Consortium. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst Sep;94(18): Tai YC et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst Dec;99(23): Ford D et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. Mar;62(3):676-89, Biron-Shental T et al. High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma. Eur J Surg Oncol. Dec;32(10): ,

11 26. Ozcelik H et al. Germline BRCA26174delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet. May;16(1):17-8, The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. Aug;91(15):1310-6, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ): Genetic/Familial High-Risk Assessment: Colorectal. Version Retrieved June 4, 2014 from asp#genetics_ colon 29. Kohlmann W et al. Lynch Syndrome Feb 5 [Updated 2012 Sept 20]. In: Pagon RA, Adam MP, Bird TD, et al., (Eds), GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; Quehenberger F, Vasen HF, van Houwelingen HC. Risk of colorectal and endometrial cancer for carriers of mutations of the hmlh1 and hmsh2 gene: Correction for ascertainment. J Med Genet. 42(6): , Vasen HF et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 110(4): , Dowty JG et al. Cancer risks for MLH1 and MSH2 mutation carriers. Hum Mutat. 34(3): , Bonadona V et al. Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6 Genes in Lynch Syndrome. JAMA. 305(22): , Baglietto L et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 102(3): , Senter L et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 135(2): , Kempers MJ et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: A cohort study. Lancet Oncol. 12(1):49-55, Casadei S, Norquist BM, Walsh T et al. Contribution to familial breast cancer of inherited mutations in the BRCA2- interacting protein PALB2. Cancer Res. 2011;71(6): Erkko H et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature 2007;446: Rahman N et al. PALB2, which encodes a BRCA2-interacting protein is a breast cancer susceptibility gene. Nat Genet. 2007;39(2): Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian cancer, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. PNAS 2011;108:18032, Renwick A, Thompson D, Seal S, et al. ATM Mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38(8):873, Thompson D, Duedal S, Kirner J, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97:813, Roberts NJ, Jio Y, Yu J, et al. ATM mutations in patients with hereditary pancreatic cancer. Cancer Discovery 2(1):41, Gonzalez KD, Buzin CH, Noltner KA, et al. High frequency of de novo mutations in Li-Fraumeni syndrome. J Med Genet 46:689, Ruijs MWG, Verhoef S, Rookus MA, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: Mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet 47: , Chompret A et al. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer. 82(12):1932-7, Olivier M et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 63(20): , Goldstein AM et al. High-risk Melanoma Susceptibility Genes and Pancreatic Cancer, Neural System Tumors, and Uveal Melanoma across GenoMEL. Cancer Res. Oct 15;66(20): , Puntervoll HE et al. Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants. J Med Genet. Apr;50(4):264-70, Park DJ et al. Rare mutations in XRCC2 increase the risk of breast cancer. Am J Hum Genet. Apr 6;90(4):734-9, Lin WY et al. A role for XRCC2 gene polymorphisms in breast cancer risk and survival. J Med Genet. Jul;48(7):477-84, Jiao L et al. XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer. Am J Gastroenterol. Feb;103(2):360-7, Hansen CB et al. Clinical germline genetic testing for melanoma. Lancet Oncol 2004; 5: Canto MI et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 2013; 62(3): NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ): Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version Retrieved June 4, 2014 from asp#genetics_colon 56. Frantzen C. et al. Von Hippel-Lindau Disease (2012, June 21). Retrieved October 16, 2013 from: nih. gov/books/nbk1463/ nih.gov/books/nbk1463/ CLINICIAN GUIDE FOR HEREDITARY PANCREATIC CANCER 10

12 How can I order this test? You can order this test by taking the following steps: 1. Download the OncogeneDx test requisition form from the GeneDx website: 2. Complete all the forms with required information 3. Ship completed forms along with two 4mL lavender top tubes of blood samples per person to the following address: Accessions GeneDx 207 Perry Parkway Gaithersburg, MD We provide shipping kits to physicians upon request. To place an order for shipping kits, please visit our website: or us at: wecare@genedx.com About GeneDx GeneDx is a highly respected genetic testing company founded in 2000 by two scientists from the National Institutes of Health (NIH) to address the needs of patients and clinicians concerned with rare inherited disorders. GeneDx offers sequencing and deletion/duplication testing for inherited cardiac disorders, mitochondrial disorders, neurological disorders, inherited cancer disorders, prenatal disorders and other rare genetic disorders. GeneDx also offers whole exome sequencing, next-generation and microarray-based testing. At GeneDx, our technical services are matched by our scientific expertise and customer support. Our growing staff includes more than 70 geneticists and genetic counselors specialized in clinical genetics, molecular genetics, metabolic genetics and cytogenetics who are just a phone call or away. We invite you to visit our website: to learn more about us and the services we offer. 207 Perry Parkway Gaithersburg, MD T F E wecare@genedx.com Information provided in this guide is current as of 11/ GeneDx. All rights reserved /14