BACKGROUND: The objective of this study was to investigate the prevalence of pathogenic germline variants (PGVs) in 32 cancer susceptibility genes in individuals with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). A key secondary objective was to evaluate how often PGVs would have been undetected with existing genetic testing criteria. METHODS: From May 2016 through May 2017, this multicenter cohort study enrolled consecutive patients aged 18 to 89 years with histologically confirmed PDAC diagnosed within the previous 12 weeks. Demographics, medical histories, and 3-generation pedigrees were collected from participants who provided samples for germline DNA analysis. RESULTS: Four hundred nineteen patients were deemed eligible, 302 were enrolled, and 298 were included in the final cohort. Clinically actionable variants were reported in 29 PDAC patients (9.7%), with 23 (7.7%) having a PGV associated with an increased risk for PDAC. Six of 23 individuals (26%) with PDAC-associated gene mutations did not meet currently established genetic testing criteria. According to guideline-based genetic testing, only 11 of the 23 PGVs (48%) in known PDAC genes would have been detected. Six additional patients (2%) had PGVs associated with an increased risk for other cancers. CONCLUSIONS: These findings support the significant prevalence of PGVs associated with PDAC and the limitations of current paradigms for selecting patients for genetic testing, and they thereby lend support for universal germline multigene genetic testing in this population.
BACKGROUND: The objective of this study was to investigate the prevalence of pathogenic germline variants (PGVs) in 32 cancer susceptibility genes in individuals with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). A key secondary objective was to evaluate how often PGVs would have been undetected with existing genetic testing criteria. METHODS: From May 2016 through May 2017, this multicenter cohort study enrolled consecutive patients aged 18 to 89 years with histologically confirmed PDAC diagnosed within the previous 12 weeks. Demographics, medical histories, and 3-generation pedigrees were collected from participants who provided samples for germline DNA analysis. RESULTS: Four hundred nineteen patients were deemed eligible, 302 were enrolled, and 298 were included in the final cohort. Clinically actionable variants were reported in 29 PDAC patients (9.7%), with 23 (7.7%) having a PGV associated with an increased risk for PDAC. Six of 23 individuals (26%) with PDAC-associated gene mutations did not meet currently established genetic testing criteria. According to guideline-based genetic testing, only 11 of the 23 PGVs (48%) in known PDAC genes would have been detected. Six additional patients (2%) had PGVs associated with an increased risk for other cancers. CONCLUSIONS: These findings support the significant prevalence of PGVs associated with PDAC and the limitations of current paradigms for selecting patients for genetic testing, and they thereby lend support for universal germline multigene genetic testing in this population.
Authors: Toshiya Abe; Amanda L Blackford; Koji Tamura; Madeline Ford; Patrick McCormick; Miguel Chuidian; Jose Alejandro Almario; Michael Borges; Anne Marie Lennon; Eun Ji Shin; Alison P Klein; Ralph H Hruban; Marcia I Canto; Michael Goggins Journal: J Clin Oncol Date: 2019-03-18 Impact factor: 44.544
Authors: Danielle Hutchings; Zhengdong Jiang; Michael Skaro; Matthew J Weiss; Christopher L Wolfgang; Martin A Makary; Jin He; John L Cameron; Lei Zheng; David S Klimstra; Randall E Brand; Aatur D Singhi; Michael Goggins; Alison P Klein; Nicholas J Roberts; Ralph H Hruban Journal: Mod Pathol Date: 2019-07-08 Impact factor: 7.842
Authors: Mary Linton B Peters; Andrew Eckel; Anna Lietz; Claudia Seguin; Peter Mueller; Chin Hur; Pari V Pandharipande Journal: Pancreatology Date: 2022-05-31 Impact factor: 3.977
Authors: Parisa Momtaz; Catherine A O'Connor; Joanne F Chou; Marinela Capanu; Wungki Park; Chaitanya Bandlamudi; Michael F Berger; David P Kelsen; Sarah P Suehnholz; Debyani Chakravarty; Kenneth H Yu; Anna M Varghese; Alice Zervoudakis; Jia Li; Geoffrey Y Ku; Jennifer S Park; Marina Shcherba; James J Harding; Zoe Goldberg; Ghassan K Abou-Alfa; Erin E Salo-Mullen; Zsofia K Stadler; Christine A Iacobuzio-Donahue; Eileen M O'Reilly Journal: Cancer Date: 2021-08-05 Impact factor: 6.921