Dr. Matthew Yurgelun on Pathogenic Mutations in CRC

Matthew B. Yurgelun, MD, Targeted Oncology, Yurgelun, Instructor in Medicine, Harvard Medical School, discusses a recent study which uncovered BRCA1 and BRCA2 mutations as possible risk markers for colorectal cancer.

The study examined 1000 individuals with colorectal cancer who were seen at the Dana Farber Cancer Institute. The goal of the study was to try and understand what the prevalence of hereditary cancer susceptibility syndromes was in this patient population.

It was determined that 10% of patients in the cohort had pathogenic mutations in one or more cancer susceptibility genes. There was a 3.1% prevalence of Lynch syndrome, which fits with what has been seen in established literature, says Yurgelun. Virtually all of the patients who had Lynch syndrome had tumors with high-level microsatellite instability and mismatch repair deficiency, illustrating that the current processes for identifying Lynch syndrome among colorectal cancer patients seems to work

What was novel about the study however, was that 7.1% of patients with colorectal cancer had a mutation in the non-Lynch syndrome cancer susceptibility gene, says Yurgelun. These are patients who wouldn't be picked up by typical tumor testing, as tumor testing really just looks for evidence of Lynch syndrome. The most common high-penetrance finding in the cohort beyond Lynch syndrome was, surprisingly, mutations in BRCA1 and BRCA2, says Yurgelun. These are genes that are not traditionally linked to risks of colorectal cancer.