Incidental MSH6 Germline Pathogenic Variant Identified through Tumor-only Comprehensive Genomic Profiling in a Patient with Small Cell Lung Cancer.
Hideto Ishimoto, Mikako Miyata, Chiyomi Otsuka et al.
✦ AI-curated · Sources linked
Case in brief
A 55-year-old woman with limited-disease small cell lung cancer had a partial response to first-line chemotherapy, followed by recurrence after one year. Comprehensive genomic profiling during second-line therapy detected an MSH6 frameshift variant. Mismatch repair protein expression was retained in the lung tumor, but review of her earlier colon cancer specimen showed loss of MSH6 and deficient mismatch repair. Germline testing confirmed Lynch syndrome, and cascade testing found the same variant in her daughter.
What made this case unusual
The lung tumor retained MSH6 expression despite the germline MSH6 variant; the prior colon cancer specimen provided evidence of mismatch repair deficiency.
Diagnostic / clinical pearl
A variant detected on tumor-only genomic profiling may warrant germline confirmation; discordant findings across tumors can inform interpretation.
Why it matters
The case also illustrates that confirmation of a germline finding can enable cascade testing of at-risk relatives.