TY - JOUR
T1 - GBM-associated mutations and altered protein expression are more common in young patients
AU - Ferguson, Sherise D.
AU - Xiu, Joanne
AU - Weathers, Shiao Pei
AU - Zhou, Shouhao
AU - Kesari, Santosh
AU - Weiss, Stephanie E.
AU - Verhaak, Roeland G.
AU - Hohl, Raymond J.
AU - Barger, Geoffrey R.
AU - Reddy, Sandeep K.
AU - Heimberger, Amy B.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Adult
KW - Age Factors
KW - Aged
KW - Aging/genetics
KW - Biomarkers, Tumor/genetics
KW - Brain Neoplasms/genetics
KW - Cohort Studies
KW - DNA Methylation
KW - DNA Mutational Analysis/methods
KW - ErbB Receptors/genetics
KW - Gene Expression Regulation, Neoplastic
KW - Glioblastoma/genetics
KW - Humans
KW - Mutation
KW - Tumor Suppressor Protein p53/genetics
UR - https://www.scopus.com/pages/publications/84994235283
U2 - 10.18632/oncotarget.11617
DO - 10.18632/oncotarget.11617
M3 - Article
C2 - 27579614
AN - SCOPUS:84994235283
SN - 1949-2553
VL - 7
SP - 69466
EP - 69478
JO - Oncotarget
JF - Oncotarget
IS - 43
ER -