New insights on familial colorectal cancer type X syndrome

Familial colorectal cancer type X (FCCTX) is a heterogeneous colorectal cancer predisposition syndrome that, although displays a cancer pattern similar to Lynch syndrome, is mismatch repair proficient and does not exhibit microsatellite instability. Besides, its genetic etiology remains to be elucidated. In this study we performed germline exome sequencing of 39 cancer-affected patients from 34 families at risk for FCCTX. Variant classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic/likely pathogenic variants were identified in 17.65% of the families. Rare and potentially pathogenic alterations were identified in known hereditary cancer genes (CHEK2), in putative FCCTX candidate genes (OGG1 and FAN1) and in other cancer-related genes such as ATR, ASXL1, PARK2, SLX4 and TREX1. This study provides novel important clues that can contribute to the understanding of FCCTX genetic basis.

Automated summary

Family colorectal cancer type X (FCCTX) is a heterogeneous colorectal cancer predisposition syndrome with unknown genetic etiology. This study conducted germline exome sequencing on cancer-affected patients from families at risk for FCCTX, and identified rare and potentially pathogenic variants in known hereditary cancer genes, putative FCCTX candidate genes, and other cancer-related genes. These findings provide important clues for understanding the genetic basis of FCCTX.