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

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Pancreatic neuroendocrine neoplasms (pNENs) represent the second most frequent pancreatic malignancy.
• The contribution of germline DNA repair gene mutations to pNEN pathogenesis is not well understood.
• Hereditary and sporadic cancers are often driven by germline mutations in DNA repair genes.

Purpose of the Study:

• To determine the frequency of germline DNA repair gene mutations in patients with pNENs.
• To evaluate the clinical relevance of these mutations, considering family cancer history.
• To explore the potential role of germline DNA repair gene variants in pNEN development.

Main Methods:

• Targeted next-generation sequencing was used to analyze germline DNA from 57 Polish pNEN patients.
• A panel of DNA repair genes was screened for variants.
• Variant classification adhered to American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines.

Main Results:

• Germline mutations were detected in 14 out of 57 patients (24.6%), irrespective of family cancer history.
• Pathogenic variants in BRCA2 and CHEK2 were identified in two patients.
• Seven patients had variants of uncertain significance (VUS) in DNA repair genes implicated in various cancers.

Conclusions:

• Germline mutations in DNA repair genes may play a role in the development of pNENs, even in individuals without a known family history of cancer.
• These genetic alterations are associated with other cancer types, highlighting a potential shared genetic susceptibility.
• Further research, including broader germline testing and population-specific studies, is warranted to fully elucidate the genetic landscape and clinical impact of these findings.