ArticlePloS one2013
Integrated analysis of mismatch repair system in malignant astrocytomas.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Assessment of the Type and Degree of Genomic Instability in Gliomas.International journal of molecular sciences · 2026Article
- Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review).Molecular and clinical oncology · 2024Review
- Immunohistochemical screening for mismatch repair protein deficiency in paediatric high-grade gliomas - institutional experience and review of literature.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Review
- Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1.Journal of neuro-oncology · 2020Article
- Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation.Journal of cellular and molecular medicine · 2019Article
- Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.Oncology letters · 2017Article
- Immune Checkpoint Inhibitors in Gliomas.Current oncology reports · 2017Review
- Mismatch Repair Deficiency and Response to Immune Checkpoint Blockade.The oncologist · 2016Review
- Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients.International journal of molecular sciences · 2016Article
- Association of MSH6 mutation with glioma susceptibility, drug resistance and progression.Molecular and clinical oncology · 2016Article
- Genetic counseling and tumor predisposition in neuro-oncology practice.Neuro-oncology practice · 2016Review
- Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment.Acta neuropathologica · 2015Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI) and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.
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