GBM-associated mutations and altered protein expression are more common in young patients

Sherise D. Ferguson*, Joanne Xiu, Shiao Pei Weathers, Shouhao Zhou, Santosh Kesari, Stephanie E. Weiss, Roeland G. Verhaak, Raymond J. Hohl, Geoffrey R. Barger, Sandeep K. Reddy, Amy B. Heimberger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: Geriatric glioblastoma (GBM) patients have a poorer prognosis than younger patients, but IDH1/2 mutations (more common in younger patients) confer a favorable prognosis. We compared key GBM molecular alterations between an elderly (age ≥ 70) and younger (18 < = age < = 45) cohort to explore potential therapeutic opportunities. Results: Alterations more prevalent in the young GBM cohort compared to the older cohort (P < 0.05) were: overexpression of ALK, RRM1, TUBB3 and mutation of ATRX, BRAF, IDH1, and TP53. However, PTEN mutation was significantly more frequent in older patients. Among patients with wild-type IDH1/2 status, TOPO1 expression was higher in younger patients, whereas MGMT methylation was more frequent in older patients. Within the molecularly-defined IDH wild-type GBM cohort, younger patients had significantly more mutations in PDGFRA, PTPN11, SMARCA4, BRAF and TP53. Methods: GBMs from 178 elderly patients and 197 young patients were analyzed using DNA sequencing, immunohistochemistry, in situ hybridization, and MGMT-methylation assay to ascertain mutational and amplification/expressional status. Conclusions: Significant molecular differences occurred in GBMs from elderly and young patients. Except for the older cohort's more frequent PTEN mutation and MGMT methylation, younger patients had a higher frequency of potential therapeutic targets.

Original languageEnglish (US)
Pages (from-to)69466-69478
Number of pages13
JournalOncotarget
Volume7
Issue number43
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • DNA sequencing
  • GBM
  • Mutational analysis

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'GBM-associated mutations and altered protein expression are more common in young patients'. Together they form a unique fingerprint.

Cite this