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.

Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome

“…Furthermore, we showed that ALK overexpression is more common in older individuals (>59 years) with IDH1 R132H -negative GBM in keeping with data indicating that the molecular profile of GBM differs between younger and older patients 30. In a recent study assessing ALK expression by immunohistochemistry, no significant difference between young (<45 years) and older (>70 years) patients was reported in 44 IDH1 R132H -negative GBM, but when all GBM (n=48) were evaluated ALK positivity was more prevalent in the younger group 31.…”

Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation, MGMT Promoter Methylation, and TERT Mutation Status: Experience from a Tertiary Care Center in India

“…For TP53 mutational analysis, coding regions from exons 2 to 11 were evaluated using the direct sequencing protocol as described in the International Agency for Research on Cancer p53 database and described earlier [14]. Mutations in exon 4 of IDH1 were determined by direct sequencing in all the cases as described in the previous study [15].…”

Histopathological Features of Common Pediatric Brain Tumors

“…Mutations in H3.3 were also highly specifi c for GBMs when compared to low-grade lesions and thus provide additional tools to help differentiate between the different tumor grades in small biopsies [ 11 ]. Although extremely rare in the pediatric population, IDH1 mutations may be encountered in the adolescent age group [ 12 ].…”