Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms

Abstract

PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma

“…8 Recently, a high prevalence of germline mutations (19%) in exocrine pancreatic cancer was reported by Lowery et al 23 However, 20% of the study population was Ashkenazi and accounted for one-third of the pathogenic mutations identified, which may have contributed to the high frequency of mutations. 8 Recently, a high prevalence of germline mutations (19%) in exocrine pancreatic cancer was reported by Lowery et al 23 However, 20% of the study population was Ashkenazi and accounted for one-third of the pathogenic mutations identified, which may have contributed to the high frequency of mutations.…”

Family communication and patient distress after germline genetic testing in individuals with pancreatic ductal adenocarcinoma

“…Germline pathogenic variants have been identified in 4% to 19% of patients with pancreatic ductal adenocarcinoma (PDAC) . This finding has sparked robust discussion regarding the potential role of more frequent germline genetic testing in this population, and the National Comprehensive Cancer Network recently updated its BRCA1/2 testing criteria to include any individual diagnosed with pancreatic cancer, regardless of personal or family history .…”

Ampullary cancer: Evaluation of somatic and germline genetic alterations and association with clinical outcomes

“…Current therapy and PGA screening for AC are extrapolated primarily from pancreatic, biliary, and colorectal cancer treatment and management, in part because the primary pathologic subtypes of AC are intestinal and pancreaticobiliary. Furthermore, there is a growing literature demonstrating that a multitude of solid tumors harbor PGAs . These findings suggest that PGAs are not limited to a specific type of cancer but are perhaps a pan‐cancer observation.…”

“…We determined the total and allele‐specific copy number from the sequence coverage and genotypes of polymorphic single‐nucleotide polymorphisms across the genomes that could identify regions of LOH with the Fraction and Allele‐Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm. The tumor zygosity of each PGA was inferred in the tumor according to its variant allele fraction and the FACETS segment on which it occurred …”

“…Targeted therapies based on genetic profiling have been gaining traction for other gastrointestinal malignancies such as colon, pancreatic, and biliary malignancies . For example, pathogenic germline alterations (PGAs) in DNA repair genes such as BRCA1/2 , ATM , and PALB2 have been implicated in pancreatic cancer as targets for therapy, as a way to prognosticate patients, and as a way to identify at‐risk family members . Specifically, platinum agents and poly adp (adenosine diphosphate ribose) polymerase (PARP) inhibitors are thought to be synthetically lethal to tumor cells in patients with BRCA mutations and perhaps other PGAs present in the DNA repair pathway .…”