title: Characterization of molecular genetic alterations in GBMs highlights a distinctive molecular profile in young adults.
abstract: To evaluate age-related differences in histopathologic and molecular profile of glioblastomas (GBMs) at various age groups, with special reference to TP53 mutation, epidermal growth factor receptor (EGFR) amplification, EGFR vIII mutant, PTEN deletion, and IDH1 mutation. Agewise GBM incidence was calculated over a period of 5 years (2005 to 2009). Seventy-five GBMs were selected for molecular analysis. Majority of cases were in the age group of 41 to 60 years, and mean age was 43.6 years. Histology of all 75 cases selected for molecular profiling was identical. Primary adult GBMs showed EGFR amplification and PTEN deletion in majority (37.3% and 54.9%, respectively). TP53 and IDH1 mutations were rare (11.8% cases each). In secondary GBMs, TP53 (66.7%) and IDH1 mutations (44.4%) were most frequent. PTEN deletion was seen in 33.3% and none had EGFR amplification. Pediatric GBMs (<18 y) harbored frequent TP53 mutations (46.7%) and PTEN deletion in 40%. IDH1 mutations and EGFR amplification were absent. The molecular profile of primary GBMs in young adults (19 to 40 y) was distinctly different from that of adults older than 40 years. TP53 mutation was present in 20% cases. The frequency of EGFR amplification (13.3%) and PTEN deletion (33.3%) was significantly low (P=0.028 and 0.046, respectively). IDH1 mutation, which is rare in primary adult GBMs, was present in 40% of cases. Molecular heterogeneity exists within GBMs of different age cohorts. The molecular profile of GBMs in young adults is distinctly different. Thus, there is a strong need for further studies in various age groups to provide guidelines for therapeutic targeting.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Prerana
authors.initials: P
authors.lastname: Jha
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.forename: Geetika
authors.initials: G
authors.lastname: Singh
authors.forename: Pankaj
authors.initials: P
authors.lastname: Jha
authors.forename: Suvendu
authors.initials: S
authors.lastname: Purkait
authors.forename: Pankaj
authors.initials: P
authors.lastname: Pathak
authors.forename: Vikas
authors.initials: V
authors.lastname: Sharma
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
authors.forename: Ashish
authors.initials: A
authors.lastname: Suri
authors.forename: Deepak
authors.initials: D
authors.lastname: Gupta
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Mahapatra
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002869:Chromosome Aberrations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D014644:Genetic Variation; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human