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.
N1 - Funding Information:
The authors thank Audria Patrick and David M. Wildrick, Ph. D., for their administrative and editorial support. This research was funded by the Dr. Marnie Rose Foundation and the National Institutes of Health CA 1208113, P50 CA127001, and P30 CA016672.
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.
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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 -