Introduction and Aims Surveillance is recommended for High-Risk Individuals (HRI) who are predisposed to pancreatic ductal adenocarcinoma (PDAC), because of familial (i.e., genetic) predisposition. All individuals under consideration for such surveillance in the UK, are registered and risk scored by the European Registry for Hereditary Pancreatic Diseases (EUROPAC). We generated a family risk score (FR) to optimize pancreatic cancer surveillance, started using this in 2020 and have recently validated it. Our aim was to combine this score with germline DNA analysis from both candidates and affected family members to form improved and distinct groups for surveillance. Methods Thermo-Fischer™ Ion AmpliSeq Custom Targeted NGS Panel of 43 genes, was undertaken on participant samples. Genes selected were based on known associations with germline cancer predisposition or overlapping gene ontology with cancer predisposition genes. Variants discovered were classified according to their pathogenicity. Results Between 1st April 2022 and 1st December 2025, 271 individuals samples underwent analysis. 37 participants showed 38 mutations with sufficient complexity to require both check analysis and additional discussion at the Geno-Phenotype Multi-Disciplinary Team. In 26 (26/271; 10%) of these, a mutation was detected which either directly affected surveillance or affected outcomes. All gene variants were subjected to oversight by authors who can interpret both their genetic and clinical importance. Of note our deep genomic search discovered nine variants which are currently unavailable on the NHS or National Comprehensive Cancer Network. Conclusions Comprehensive genomic analysis of families at risk of developing PDAC, better identifies those individuals in need of surveillance.
Hopley et al. (Fri,) studied this question.
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