Genomic analysis revealing Lynch syndrome in a case of high-grade glioma: illustrative case

• DOI: 10.3171/case24718
• Publication Date: 2025-03-03T06:54:09Z
• Authors: Shinichiro Koizumi; Moriya Iwaizumi; Satoshi Baba; Mineko Ushiama; Makoto Hirata; Kazuhiko Kurozumi

BACKGROUND Advances in cancer genome analysis technology have made individual cancer genome profiling (CGP) possible. CGP can indicate the presence of hereditary tumors, which are caused by germline pathogenic variants in oncogenes or tumor suppressor genes; if a hereditary tumor is suspected, multigene panel testing (MGPT) is performed. Genomic medicine thus plays an important role in diagnosing hereditary tumors.

OBSERVATIONS A 41-year-old man presented with headache and depressive symptoms. Close examination revealed a mass lesion with cystic components in the right parietal lobe. The tumor was removed via craniotomy and was pathologically diagnosed as a high-grade glioma. CGP of the tumor area revealed a high tumor mutation burden and multiple presumed germline pathogenic variants. MGPT of peripheral blood detected a germline pathogenic variant in MSH6. The patient was therefore diagnosed with Lynch syndrome.

LESSONS Family history and genetic risk assessments, including CGP, are important for diagnosing genetic diseases. Next-generation sequencing technology is essential for genetic analyses, and if many genetic mutations are identified using tumor-only CGP, MGPT of peripheral blood is an efficient option. In addition, MSH6 variant analysis is important for diagnosing Lynch syndrome and determining treatment. In particular, functional analysis of somatic variants is essential for understanding disease associations. https://thejns.org/doi/10.3171/CASE24718