Search

Aim: Pancreatic Neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms whose tumor biology is still little known. Thanks to next-generation sequencing, pathogenic mutations in base-excision-repair MUTYH gene and homologous recombination genes CHEK2 and BRCA2 seem to have a role in the development of pNETs. Research design & methods: We assumed that Homologous Recombination Deficiency (HRD) could be a critical pathogenetic mechanism for pNETs. We evaluated the HR status in a case series of 33 patients diagnosed with pNET at the Modena Cancer Center using the AmoyDX HRD Focus assay. Results: The AmoyDx test did not identify any HRD-positive patients (median GSS equal to 1.1, positive score: >50), and no pathogenic BRCA variants were detected. However, thanks to the SNP analysis, a consistent number of partial or complete single-copy deletions or duplications in several chromosomes. Conclusion: The AmoyDX HRD focus assay performed well on pancreatic samples, despite being originally designed for ovarian cancer and used on samples stored for over a year. Larger studies are needed to further assess the role of HRD assays in pNETs research. Article highlights Pancreatic Neuroendocrine Tumors (pNETs) are rare, heterogeneous neoplasms with limited genomic insights, particularly regarding homologous recombination deficiency (HRD). This study evaluates HRD status in a cohort of patients with pNETs, using the AmoyDX HRD Focus Assay, a cost-effective alternative to other commercially available HRD tests. The AmoyDX assay demonstrated high feasibility in analyzing formalin-fixed paraffin-embedded (FFPE) tissue samples older than 12 months, with a success rate of 93.75%. None of the 30 analyzed pNET samples tested positive for HRD, and no pathogenic variants of BRCA1 or BRCA2 were found. Three patients exhibited BRCA variants of uncertain significance (VUS). Chromosome 11 abnormalities, particularly in the MEN1 gene locus, were detected in 50% of patients, confirming the potential role of gene deletions in pNET tumorigenesis. This study contributes to the limited literature on HRD in pNETs and supports the application of HRD testing in expanding our molecular understanding of these rare tumors. [ABSTRACT FROM AUTHOR]