GBM-associated mutations and altered protein expression are more common in young patients
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Sherise D. Ferguson1, Joanne Xiu4, Shiao-Pei Weathers2, Shouhao Zhou3, Santosh Kesari5, Stephanie E. Weiss6, Roeland G. Verhaak7, Raymond J. Hohl8, Geoffrey R. Barger9, Sandeep K. Reddy4, Amy B. Heimberger1
1Department of Neurosurgery, Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
2Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
3Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
4Caris Life Sciences, Phoenix, AZ 85040, USA
5Department of Translational Neuro-Oncology and Neurotherapeutics, Pacific Neuroscience Institute and John Wayne Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA 90404, USA
6Fox Chase Cancer Center, Philadelphia, PA 19111, USA
7Department of Genome Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA
8Penn State Hershey Cancer Institute, Hershey, PA 17033, USA
9Department of Neurology, Wayne State University, School of Medicine, Karmanos Cancer Center, Detroit, MI 48201, USA
Sherise D. Ferguson, email: email@example.com
Joanne Xiu, email: JXIU@CARISLS.COM
Keywords: GBM, mutational analysis, DNA sequencing
Received: June 19, 2016 Accepted: August 15, 2016 Published: August 25, 2016
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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