A researcher studying colorectal carcinogenesis finds that epigenetic silencing of MLH1 by promoter hypermethylation leads to microsatellite instability (MSI-H) without germline mutation. This sporadic mechanism is distinct from Lynch syndrome. In what percentage of sporadic MSI-H colorectal cancers is MLH1 silencing caused by BRAF V600E mutation-associated epigenetic reprogramming?
- A About 10%
- B About 80% ✓
- C About 40%
- D Virtually 100%
Correct answer: B. About 80%
Explanation
Approximately 80% of sporadic MSI-H colorectal cancers harbor BRAF V600E mutation, which is closely linked to the CpG island methylator phenotype (CIMP) and epigenetic silencing of MLH1. This BRAF mutation is essentially never found in Lynch syndrome-associated colorectal cancers, making BRAF V600E testing a useful discriminator between sporadic MSI-H tumors and Lynch syndrome. The methylation is driven by the BRAF-MAPK pathway altering the epigenome of colonocytes.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.