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Related Experiment Video

Updated: Feb 22, 2026

Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation

Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation

Published on: January 14, 2014

Germline MSH6 Mutation in a Patient With Two Independent Primary Glioblastomas.

Linda M Forsström¹, Koichiro Sumi¹, Markus J Mäkinen¹

¹Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland; Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland; International Agency for Research on Cancer, Lyon, France; Department of Pathology, Oulu University Hospital, Oulu, Finland; Medical Faculty, University of Zurich, Zurich, Switzerland.

Journal of Neuropathology and Experimental Neurology

|September 20, 2017

Summary

A patient developed two independent glioblastomas due to a germline MSH6 mutation. Loss of MSH6 gene function was critical in the development of both primary brain tumors.

Keywords:

Exome sequencing Germline mutation Glioblastoma MSH6

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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells

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Published on: November 28, 2015

Area of Science:

Neuro-oncology
Cancer Genetics
Molecular Biology

Background:

Glioblastoma is an aggressive primary brain tumor.
Developing two distinct glioblastomas is rare and poses diagnostic challenges.
Understanding the molecular basis of multiple primary tumors is crucial for patient outcomes.

Observation:

A patient presented with two glioblastomas, 10 years apart, in different brain hemispheres.
Genetic analysis revealed discordant TP53 and PTEN mutations, suggesting independent tumor origins.
Both tumors were IDH-wildtype, ruling out secondary glioblastoma development from precursor lesions.

Findings:

Whole-exome sequencing identified a germline heterozygous mutation in the MSH6 mismatch repair gene.
The first glioblastoma exhibited loss of the wild-type MSH6 allele.
The second glioblastoma had a somatic mutation in the MSH6 gene.
Both glioblastomas demonstrated biallelic inactivation of MSH6, leading to loss of function.

Implications:

Loss of MSH6 function is implicated as a key driver in the pathogenesis of these two independent primary glioblastomas.
This case highlights the role of mismatch repair gene mutations in the development of multiple primary brain tumors.
Germline MSH6 mutations should be considered in patients with multiple primary glioblastomas, even in the absence of typical hereditary cancer syndromes.