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Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors
- Source :
- Laboratory Investigation; a Journal of Technical Methods and Pathology
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Mismatch repair-deficient (MMRD) brain tumors are rare among primary brain tumors and can be induced by germline or sporadic mutations. Here, we report 13 MMRD-associated (9 sporadic and 4 Lynch syndrome) primary brain tumors to determine clinicopathological and molecular characteristics and biological behavior. Our 13 MMRD brain tumors included glioblastoma (GBM) IDH-wildtype (n = 9) including 1 gliosarcoma, astrocytoma IDH-mutant WHO grade 4 (n = 2), diffuse midline glioma (DMG) H3 K27M-mutant (n = 1), and pleomorphic xanthoastrocytoma (PXA) (n = 1). Next-generation sequencing using a brain tumor-targeted gene panel, microsatellite instability (MSI) testing, Sanger sequencing for germline MMR gene mutation, immunohistochemistry of MMR proteins, and clinicopathological and survival analysis were performed. There were many accompanying mutations, suggesting a high tumor mutational burden (TMB) in 77%, but TMB was absent in one case of GBM, IDH-wildtype, DMG, and PXA, respectively. MSH2, MLH1, MSH6, and PMS2 mutations were found in 31%, 31%, 31% and 7% of patients, respectively. MSI-high and MSI-low were found in 50% and 8% of these gliomas, respectively and 34% was MSI-stable. All Lynch syndrome-associated GBMs had MSI-high. In addition, 77% (10/13) had histopathologically multinucleated giant cells. The progression-free survival tended to be poorer than the patients with no MMRD gliomas, but the number and follow-up duration of our patients were insufficient to get statistical significance. In the present study, we found that the most common MMRD primary brain tumor was GBM IDH-wildtype. The genetic profile of MMRD GBM was different from that of conventional GBM. MMRD gliomas with TMB and MSI-H may be sensitive to immunotherapy but resistant to temozolomide. Our findings can help develop better treatment options.<br />The authors examined 13 mismatch repair-deficient (MMRD)-associated primary brain tumors to determine molecular characteristics and biological behavior. MMRD occurred after chemotherapy and radiotherapy in two cases. The genetic profile of MMRD glioblastoma was different from that of conventional glioblastoma. Half of the MMRD-gliomas and all Lynch syndrome-associated GBMs were high in microsatellite instability. These tumors had high mutational burdens and tended to have shorter progression-free survival than glioma without MMRD.
- Subjects :
- Adult
Male
congenital, hereditary, and neonatal diseases and abnormalities
Gliosarcoma
Adolescent
Brain tumor
Gene mutation
DNA Mismatch Repair
Article
Pathology and Forensic Medicine
Glioma
Biomarkers, Tumor
Temozolomide
Cancer genomics
medicine
Humans
Child
Antineoplastic Agents, Alkylating
neoplasms
Molecular Biology
Oncogenesis
Aged
Brain Neoplasms
business.industry
Brain
High-Throughput Nucleotide Sequencing
Microsatellite instability
Astrocytoma
Cell Biology
Middle Aged
medicine.disease
Colorectal Neoplasms, Hereditary Nonpolyposis
Magnetic Resonance Imaging
digestive system diseases
Lynch syndrome
Pedigree
nervous system diseases
Mutation
Cancer research
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 00236837
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- Laboratory Investigation
- Accession number :
- edsair.doi.dedup.....8626c33b0e388b862e80c1f1529157b1