ArticleCancer research2006
A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy.
Article in Cancer research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers.
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Who cites it
252 citing papers in PubMed, 432 citations in OpenAlex.
- Temozolomide Treatment Alters Mismatch Repair and Boosts Mutational Burden in Tumor and Blood of Colorectal Cancer Patients.Cancer discovery · 2022Trial
- Temozolomide Followed by Combination With Low-Dose Ipilimumab and Nivolumab in Patients With Microsatellite-Stable, OJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01).Neuro-oncology · 2020Trial
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- The Imbalance Between Tumor Immunosurveillance and Tumor Immune Escape in Glioblastoma.Immunology and cell biology · 2026Review
- Clinical Impact of MGMT Promoter Methylation in IDH-Mutant Gliomas: Influence of Threshold Selection and Clinical Confounding.Annals of clinical and translational neurology · 2026Article
- The intersection of chemokine signaling with the hallmarks of cancer in glioblastoma.Journal of neuro-oncology · 2026Review
- Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.International journal of radiation oncology, biology, physics · 2026Review
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- Chloroethylnitrosourea analogue HJ03 overcomes temozolomide resistance of glioblastoma in mice through induction of ferroptosis and apoptosis.Acta pharmacologica Sinica · 2026Article
- Beyond Darwin: reactive heredity, burst-drift dynamics and eco‑evolutionary control of cancer.Molecular cancer · 2026Review
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- Glioblastoma: epidemiology, molecular pathogenesis, diagnosis, management, and therapeutic resistance.Molecular biomedicine · 2026Review
- Molecular and clinical characteristics of glioma patients with germline pathogenic mutations of Lynch syndrome genes: a large-scale multicenter study.Journal of translational medicine · 2026Article
- Distinct mutational signature and clonal evolution in constitutional mismatch repair deficiency-associated high-grade gliomas.iScience · 2026Article
- Acquired High Tumor Mutational Burden and Activity of Immunotherapy after Targeted Therapy in Microsatellite Stable Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Distinct molecular pathways leading to dosage-dependent temozolomide resistance in GBM stem cells.Cancer cell international · 2026Article
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- Review
- Mismatch Repair Deficiency in Gliomas: A Rare Insight into Microsatellite Instability and Its Diagnostic Implications.Asian journal of neurosurgery · 2025Article
192 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
55 authors at 7 institutions in 2 countries.
Funding
Abstract
Malignant gliomas have a very poor prognosis. The current standard of care for these cancers consists of extended adjuvant treatment with the alkylating agent temozolomide after surgical resection and radiotherapy. Although a statistically significant increase in survival has been reported with this regimen, nearly all gliomas recur and become insensitive to further treatment with this class of agents. We sequenced 500 kb of genomic DNA corresponding to the kinase domains of 518 protein kinases in each of nine gliomas. Large numbers of somatic mutations were observed in two gliomas recurrent after alkylating agent treatment. The pattern of mutations in these cases showed strong similarity to that induced by alkylating agents in experimental systems. Further investigation revealed inactivating somatic mutations of the mismatch repair gene MSH6 in each case. We propose that inactivating somatic mutations of MSH6 confer resistance to alkylating agents in gliomas in vivo and concurrently unleash accelerated mutagenesis in resistant clones as a consequence of continued exposure to alkylating agents in the presence of defective mismatch repair. The evidence therefore suggests that when MSH6 is inactivated in gliomas, alkylating agents convert from induction of tumor cell death to promotion of neoplastic progression. These observations highlight the potential of large scale sequencing for revealing and elucidating mutagenic processes operative in individual human cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.