Exome & General Genetics

Session # 1501

Germline Genetic Testing in Unselected Pancreatic Ductal Adenocarcinoma (PDAC) Patients.

  • The study presents data on cases unselected for age at diagnosis or family history representing a typical population of pancreatic cancer patients that present for clinical care.
  • Pancreatic cancer predisposition associated with known syndromes such as HBOC or Lynch Syndrome account for a fraction of the potentially hereditary cases.
  • Current genetic testing criteria for pancreatic cancer may not be sensitive to the remaining fraction of hereditary cases that are related to genes such as ATM and CHEK2


Background: The aim of this study is to assess the prevalence of known heritable germline mutations in unselected PDAC patients and to determine how well current guidelines for genetic testing identify mutation carriers.   Methods:  Consecutive, unselected patients with recently diagnosed PDAC from three centers were enrolled from May to December 2016 in an ongoing prospective study.  A three­generation pedigree was obtained.  Germline mutations in 12 genes associated with PDAC risk (APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, PALB2, PMS2, STK11, TP53) and in 19 genes related to other cancer risks were screened for by NGS. American College of Gastroenterology and NCCN criteria for genetic testing for BRCA1/2, Lynch syndrome, and Familial Pancreatic Cancer (FPC) were assessed. Results: Among 183 patients, 46% are female, 79% are Caucasian and 10% are Ashkenazi Jewish, with median (IQR) age 68 (62,75) years at diagnosis.  41% of patients met ³1 criteria for genetic testing (35.5% BRCA1/2, 2.7% Lynch, 9.3% FPC). Twenty patients (11%) were found to have a total of 21 pathogenic mutations (table). Mutation status was not associated with age at diagnosis, sex, or personal history of cancer (all p > 0.05).  Six mutation carriers (30% of positives) did not meet current criteria for genetic testing. Conclusions:  Preliminary results show that 6.6% of unselected PDAC patients carry a germline mutation in a gene known to increase PDAC risk and 4.3% have a mutation in genes not previously linked to PDAC.  Existing testing criteria did not identify 30% of carriers. Continued refinement of guidelines is necessary to align genetic testing with inherited PDAC risk.

  • Speakers: Mary Linton Bounetheau Peters; Randall Brand; Erkut Hasan Borazanci; Lindsey Stobie; Beth Dudley; Eve Karloski; James Moser; Arlene Colvin; Cynthia Lim; Nathan Bahary; Weijing Sun; John C. Rhee; Barry C. Lembersky; Ronald G. Stoller; Holly LaDuca; Jill S Dolinsky; Emily Dalton; Virginia Speare; Mary Helen Black; Nadine M. Tung
  • Conference: American Society of Clinical Oncology (ASCO)
  • Date: Friday, Jun 02, 2017 8:10am - 8:25am

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