BLM – Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is typically driven by autosomal dominant mismatch repair gene defects. BLM (a RecQ helicase) has been evaluated as a non-routine candidate in HNPCC panels, but evidence for a direct gene–disease relationship is sparse. A genome-wide LD mapping study in Ashkenazi Jews validated localization of HNPCC susceptibility to the MSH2 locus but did not implicate BLM in HNPCC risk ([PMID:15520224]). A more recent 35-gene on-demand NGS panel identified a single deleterious BLM variant among 128 hereditary breast/ovarian cancer and HNPCC cases, though details on variant recurrence, segregation, or functional validation were not provided ([PMID:32522261]).

Overall, the available data do not support a compelling role for BLM in HNPCC predisposition. No BLM variants have been observed to segregate with HNPCC in families, and no functional assays have assessed the impact of heterozygous BLM mutations on colon cancer risk or mismatch repair activity. Additional case series with segregation analyses and mechanistic studies are needed before BLM can be considered in clinical HNPCC testing panels.

References

• Cancer research • 2004 • Localization of cancer susceptibility genes by genome-wide single-nucleotide polymorphism linkage-disequilibrium mapping. PMID:15520224
• Journal of translational medicine • 2020 • A comprehensive custom panel evaluation for routine hereditary cancer testing: improving the yield of germline mutation detection. PMID:32522261

Evidence Based Scoring (AI generated)