GBM-associated mutations and altered protein expression are more common in young patients.
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.
['Ferguson|Sherise D|SD|', 'Xiu|Joanne|J|', 'Weathers|Shiao-Pei|SP|', 'Zhou|Shouhao|S|', 'Kesari|Santosh|S|', 'Weiss|Stephanie E|SE|', 'Verhaak|Roeland G|RG|', 'Hohl|Raymond J|RJ|', 'Barger|Geoffrey R|GR|', 'Reddy|Sandeep K|SK|', 'Heimberger|Amy B|AB|']
D000328:Adult D000367:Age Factors D000368:Aged D000375:Aging D014408:Biomarkers, Tumor D001932:Brain Neoplasms D015331:Cohort Studies D019175:DNA Methylation D004252:DNA Mutational Analysis D066246:ErbB Receptors D015972:Gene Expression Regulation, Neoplastic D005909:Glioblastoma D006801:Humans D009154:Mutation D016159:Tumor Suppressor Protein p53
GBM DNA sequencing mutational analysis