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IDH1 Mutations in Diffusely Infiltrating Astrocytomas Grade Specificity, Association With Protein Expression, and Clinical Relevance

Thota, Balaram and Shukla, Sudhanshu K and Srividya, Mallavarapu R and Shwetha, Shivayogi D and Arivazhagan, Arimappamagan and Thennarasu, Kandavel and Chickabasaviah, Yasha T and Hegde, Alangar S and Chandramouli, Bangalore A and Somasundaram, Kumarvel and Santosh, Vani (2012) IDH1 Mutations in Diffusely Infiltrating Astrocytomas Grade Specificity, Association With Protein Expression, and Clinical Relevance. In: AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 138 (2). pp. 177-184.

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Official URL: http://dx.doi.org/10.1309/AJCPZOIY3WY4KIKE

Abstract

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM. We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 83.3%] secondary, and 1/42 2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P < .001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P < .001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM.

Item Type: Journal Article
Keywords: Immunohistochemistry;IDH1; Astrocytoma;Somatic mutation; Prognosis;DNA sequencing;Survival
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 24 Aug 2012 05:06
Last Modified: 24 Aug 2012 05:06
URI: http://eprints.iisc.ernet.in/id/eprint/44955

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