Unexpected finding of a rare pathogenic germline BRCA1 variant in an intrahepatic cholangiocarcinoma using the Oncomine Focus DNA assay: clinical and diagnostic implications

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This study focuses on Cholangiocarcinoma (CCA), a liver cancer originating from bile duct epithelial cells and ranking as the second most common liver cancer after hepatocellular carcinoma. The institution has recently launched the Comprehensive Genomic Profiling (CGP) program, named FPG500, offering complete molecular characterization through the TruSight Oncology 500 High Throughput (TSO500HT) solution. For samples failing to meet TSO500HT’s quantity or quality requirements, they are assessed using Oncomine Focus DNA Assay (OFA) and Archer’s FusionPlex Lung Panel (AFL).

 

In the reported case, an iCCA patient enrolled in the FPG500 program underwent screening via an orthogonal workflow (OFA/AFL). Surprisingly, a pathogenic variant in the BRCA1 gene (c.5278-2del, rs878853285) was detected despite BRCA1 not being included in the OFA panel.

 

This case underscores the diagnostic potential of CGP, now widely adopted in clinical and academic settings. The incidental discovery of the BRCA1 variant highlights the role of BRCA genes in biliary tract cancers, and confirming its germline origin through orthogonal testing raises awareness of germline implications in CGP.

 

DOI: 10.1007/s11033-023-08588-x