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 Hohl, Geoffrey R. Barger, Sandeep K. Reddy, Amy B. Heimberger

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 - Jan 1 2016

Fingerprint

Glioblastoma
Mutation
Proteins
Methylation
DNA Sequence Analysis
Geriatrics
In Situ Hybridization
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Ferguson, S. D., Xiu, J., Weathers, S. P., Zhou, S., Kesari, S., Weiss, S. E., ... Heimberger, A. B. (2016). GBM-associated mutations and altered protein expression are more common in young patients. Oncotarget, 7(43), 69466-69478. https://doi.org/10.18632/oncotarget.11617
Ferguson, Sherise D. ; Xiu, Joanne ; Weathers, Shiao Pei ; Zhou, Shouhao ; Kesari, Santosh ; Weiss, Stephanie E. ; Verhaak, Roeland G. ; Hohl, Raymond ; Barger, Geoffrey R. ; Reddy, Sandeep K. ; Heimberger, Amy B. / GBM-associated mutations and altered protein expression are more common in young patients. In: Oncotarget. 2016 ; Vol. 7, No. 43. pp. 69466-69478.
@article{5d9fc6d914cf4143a1fb92a8f12359fb,
title = "GBM-associated mutations and altered protein expression are more common in young patients",
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.",
author = "Ferguson, {Sherise D.} and Joanne Xiu and Weathers, {Shiao Pei} and Shouhao Zhou and Santosh Kesari and Weiss, {Stephanie E.} and Verhaak, {Roeland G.} and Raymond Hohl and Barger, {Geoffrey R.} and Reddy, {Sandeep K.} and Heimberger, {Amy B.}",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/oncotarget.11617",
language = "English (US)",
volume = "7",
pages = "69466--69478",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "43",

}

Ferguson, SD, Xiu, J, Weathers, SP, Zhou, S, Kesari, S, Weiss, SE, Verhaak, RG, Hohl, R, Barger, GR, Reddy, SK & Heimberger, AB 2016, 'GBM-associated mutations and altered protein expression are more common in young patients', Oncotarget, vol. 7, no. 43, pp. 69466-69478. https://doi.org/10.18632/oncotarget.11617

GBM-associated mutations and altered protein expression are more common in young patients. / Ferguson, Sherise D.; Xiu, Joanne; Weathers, Shiao Pei; Zhou, Shouhao; Kesari, Santosh; Weiss, Stephanie E.; Verhaak, Roeland G.; Hohl, Raymond; Barger, Geoffrey R.; Reddy, Sandeep K.; Heimberger, Amy B.

In: Oncotarget, Vol. 7, No. 43, 01.01.2016, p. 69466-69478.

Research output: Contribution to journalArticle

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

AU - Barger, Geoffrey R.

AU - Reddy, Sandeep K.

AU - Heimberger, Amy B.

PY - 2016/1/1

Y1 - 2016/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84994235283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994235283&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.11617

DO - 10.18632/oncotarget.11617

M3 - Article

VL - 7

SP - 69466

EP - 69478

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 43

ER -