title: IDH1 mutations in gliomas: first series from a tertiary care centre in India with comprehensive review of literature.
abstract: OBJECTIVE
  Mutations of the gene encoding isocitrate dehydrogenase (IDH) have been shown in a significant proportion of diffuse gliomas. These mutations are specific to gliomas and their utility for diagnosis and prognostication of these tumors is being proclaimed. The present study was conducted with the aim of assessing frequency of IDH1 mutations in gliomas, their correlation with other molecular alterations along with a comprehensive review of available literature.
  
  
  METHODS
  A total of 100 gliomas of various grades and subtypes from Indian patients were screened for assessing frequency of IDH1 mutations. The findings were correlated with TP53 mutations, 1p/19q deletion, EGFR amplification and PTEN deletion status. The detailed comprehensive review of literature was performed comparing all studies available till date.
  
  
  RESULTS
  IDH1 mutations in codon 132 were observed in 46% cases. The frequency was 68.8% in grade II, 85.7% in grade III and 12.8% in GBMs. R132H mutation was most frequent (84.8%). Overall frequency of these mutations was relatively higher in oligodendroglial tumours as compared to astrocytic phenotype (66.7% versus 38.4%; p=0.06). Primary GBMs showed IDH1 mutation in only 4.4% cases. In contrast, 66.7% of secondary GBMs harboured this alteration. Patients with IDH1 mutations were significantly younger as compared to those without mutation (p=0.001). There was a significant correlation between IDH1 mutation and TP53 mutation (p=0.004). Although IDH1 mutation showed a positive correlation with 1p/19q deletion, the association was not statistically significant (p=0.653). There was no correlation with EGFR amplification or PTEN deletion.
  
  
  CONCLUSIONS
  IDH1 mutations are present in large proportion of Indian patients with diffuse astrocytic and oligodendroglial neoplasms similar to the reported literature form west. The frequency is lower in primary GBMs and as compared to secondary GBMs. Association with younger age and positive correlation with TP53 mutation and 1p/19q loss is observed. More importantly it is emerging as an independent prognostic marker. Hence the greatest challenge now is establishing a reliable user friendly test for incorporating this novel genetic alteration to routine clinical practice.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, Delhi, India.
authors.forename: Prerana
authors.initials: P
authors.lastname: Jha
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.forename: Vikas
authors.initials: V
authors.lastname: Sharma
authors.forename: Geetika
authors.initials: G
authors.lastname: Singh
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
authors.forename: Pankaj
authors.initials: P
authors.lastname: Pathak
authors.forename: Kunzang
authors.initials: K
authors.lastname: Chosdol
authors.forename: Pankaj
authors.initials: P
authors.lastname: Jha
authors.forename: Ashish
authors.initials: A
authors.lastname: Suri
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Mahapatra
authors.forename: Shashank Sharad
authors.initials: SS
authors.lastname: Kale
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006784:Hospitals, Teaching; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human