SCIENCE@home

Germline Mutations in DNA Repair Genes in Patients with Pancreatic Neuroendocrine Neoplasms: Diagnostic and Therapeutic Implications

B. Jurecka-Lubieniecka,Małgorzata Ros-Mazurczyk,A. Syguła,Alexander Cortez,M. Krzempek,Anna B. Tuleja,Agnieszka Kotecka-Blicharz,Marta Cieślicka,M. Oczko-Wojciechowska,D. Handkiewicz-Junak

Published 2025 in Current Oncology

ABSTRACT

Simple Summary Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after ductal adenocarcinoma. While germline mutations in DNA repair genes are known to contribute to various hereditary and sporadic cancers, their role in pNENs remains unclear. This pilot study aimed to evaluate the frequency and clinical relevance of such mutations in Polish patients with pNENs, regardless of family cancer history. Germline DNA from 57 individuals was analyzed using targeted next-generation sequencing covering a panel of DNA repair genes. Mutations were found in 14 patients (24.6%). Pathogenic variants in BRCA2 and CHEK2 were identified in two cases, while seven patients carried variants of uncertain significance (VUS). The detected alterations are associated with multiple malignancies, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings suggest that germline DNA repair gene mutations may contribute to pNEN pathogenesis, even without familial predisposition. Broader germline testing and population-specific studies are warranted. Abstract Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess the frequency and clinical relevance of germline DNA repair gene mutations in patients with pNENs, both with and without a family history of cancer. Germline DNA from 57 Polish patients with pNENs was analyzed using targeted next-generation sequencing to identify variants in a panel of DNA repair genes. Variant classification followed the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Germline mutations were identified in 14 patients (24.6%), both with and without a family history of malignancy. Two patients carried pathogenic variants in BRCA2 and CHEK2, while seven carried variants of uncertain significance (VUS). The identified variants have been implicated in various cancer types, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-82 of 82 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1