The American journal of pathology
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Microsatellite instability (MSI) has been identified in various human cancers, particularly those associated with the hereditary nonpolyposis colorectal cancer syndrome. Although gliomas have been reported in a few hereditary nonpolyposis colorectal cancer syndrome kindred, data on the incidence of MSI in gliomas are conflicting, and the nature of the mismatch repair (MMR) defect is not known. We established the incidence of MSI and the underlying MMR gene mutation in 22 patients ages 45 years or less with sporadic high-grade gliomas (17 glioblastomas, 3 anaplastic astrocytomas, and 2 mixed gliomas, grade III). ⋯ Three patients developed metachronous colorectal adenocarcinomas, fitting the criteria of Turcot's syndrome. Thus, MSI and germline MMR gene mutation is present in a subset of young glioma patients, and these patients and their family members are at risk of developing other hereditary nonpolyposis colorectal cancer syndrome-related tumors, in particular colorectal carcinomas. These results have important implications in the genetic testing and management of young patients with glioma and their families.