Incidental MSH6 Germline Pathogenic Variant Identified through Tumor-only Comprehensive Genomic Profiling in a Patient with Small Cell Lung Cancer
Abstract
A 55-year-old woman was diagnosed with limited-disease small cell lung cancer (LD-SCLC) after incidental detection of a lung nodule. First-line chemotherapy achieved partial response, but recurrence occurred after one year. During second-line therapy, comprehensive genomic profiling (CGP) revealed a germline MSH6 frameshift mutation. Although lung tumor immunohistochemistry showed the retained expression of mismatch repair (MMR) protein, a prior colon cancer specimen showed the loss of MSH6 expression and deficient MMR expression. Germline genetic testing confirmed Lynch syndrome. Cascade testing identified the same mutation in her daughter. This case outlines a tumor-to-germline workflow with testing of at-risk relatives and highlights the importance of prudent interpretation of presumed germline variants.
Related
- No Female Germline Stem Cells Were Identified by Advanced Dual Recombinase-Based Lineage Tracing System.
- Familial Multiple Trichoepitheliomas Across Three Generations With a Pathogenic CYLD Variant Identified in One Affected Family Member: A Case Report
- Case Report: Early-onset bilateral and multifocal clear cell renal cell carcinoma in a carrier of the germline likely pathogenic CHEK2 splice-region variant NM_007194.4:c.846 + 4_846 + 7del
- Colon cancer in a patient with a mosaic monoallelic germline pathogenic NF1 gene variant.
- Double heterozygous pathogenic germline APC and MSH2 variants in a 16-year-old female diagnosed with colorectal cancer
BibTeX
@article{ishimoto2026incidental,
title = {{Incidental MSH6 Germline Pathogenic Variant Identified through Tumor-only Comprehensive Genomic Profiling in a Patient with Small Cell Lung Cancer}},
author = {Hideto Ishimoto and Mikako Miyata and Chiyomi Otsuka and Mariko Koike and Saeko Nakatsubo and Shiro Adachi and Tsutomu Nishida and Naohiro Tomita},
journal = {Internal Medicine},
year = {2026},
month = sep,
doi = {10.2169/internalmedicine.6582-25},
url = {https://www.jstage.jst.go.jp/article/internalmedicine/65/18/65_6582-25/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Incidental MSH6 Germline Pathogenic Variant Identified through Tumor-only Comprehensive Genomic Profiling in a Patient with Small Cell Lung Cancer
AU - Hideto Ishimoto
AU - Mikako Miyata
AU - Chiyomi Otsuka
AU - Mariko Koike
AU - Saeko Nakatsubo
AU - Shiro Adachi
AU - Tsutomu Nishida
AU - Naohiro Tomita
PY - 2026
DA - 2026/09/15
JO - Internal Medicine
DO - 10.2169/internalmedicine.6582-25
UR - https://www.jstage.jst.go.jp/article/internalmedicine/65/18/65_6582-25/_article
AB - A 55-year-old woman was diagnosed with limited-disease small cell lung cancer (LD-SCLC) after incidental detection of a lung nodule. First-line chemotherapy achieved partial response, but recurrence occurred after one year. During second-line therapy, comprehensive genomic profiling (CGP) revealed a germline MSH6 frameshift mutation. Although lung tumor immunohistochemistry showed the retained expression of mismatch repair (MMR) protein, a prior colon cancer specimen showed the loss of MSH6 expression and deficient MMR expression. Germline genetic testing confirmed Lynch syndrome. Cascade testing identified the same mutation in her daughter. This case outlines a tumor-to-germline workflow with testing of at-risk relatives and highlights the importance of prudent interpretation of presumed germline variants.
SN - 1349-7235
SN - 0918-2918
ER -