Format

Send to

Choose Destination
Oncotarget. 2016 Apr 19;7(16):21556-69. doi: 10.18632/oncotarget.7722.

Multi-platform molecular profiling of a large cohort of glioblastomas reveals potential therapeutic strategies.

Author information

1
Caris Life Sciences, Phoenix, AZ, USA.
2
Neuro-Oncology Program, Moores Cancer Center, UC San Diego, La Jolla, CA, USA.
3
Cedars-Sinai Medical Center, Los Angeles, CA, USA.
4
Baylor University Medical Center, Dallas, TX, USA.
5
Barrow Neurological Institute, Phoenix, AZ, USA.
6
AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin, Paris, France.
7
Sorbonne Universités, UPMC Univ Paris 06, UMRS 975, Institut du Cerveau et de la Moelle, Paris, France.
8
Inserm U 975, Paris, France.
9
CNRS, UMR 7225, Paris, France.
10
Pennsylvania State University, Hershey, PA, USA.
11
Translational Neuro-Oncology Laboratories, Department of Neurosciences UC San Diego, La Jolla, CA, USA.
12
Department of Translational Neuro-Oncology and Neurotherapeutics, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.

Abstract

Glioblastomas (GBM) are the most aggressive and prevalent form of gliomas with abysmal prognosis and limited treatment options. We analyzed clinically relevant molecular aberrations suggestive of response to therapies in 1035 GBM tumors. Our analysis revealed mutations in 39 genes of 48 tested. IHC revealed expression of PD-L1 in 19% and PD-1 in 46%. MGMT-methylation was seen in 43%, EGFRvIII in 19% and 1p19q co-deletion in 2%. TP53 mutation was associated with concurrent mutations, while IDH1 mutation was associated with MGMT-methylation and TP53 mutation and was mutually exclusive of EGFRvIII mutation. Distinct biomarker profiles were seen in GBM compared with WHO grade III astrocytoma, suggesting different biology and potentially different treatment approaches. Analysis of 17 metachronous paired tumors showed frequent biomarker changes, including MGMT-methylation and EGFR aberrations, indicating the need for a re-biopsy for tumor profiling to direct subsequent therapy. MGMT-methylation, PR and TOPO1 appeared as significant prognostic markers in sub-cohorts of GBM defined by age. The current study represents the largest biomarker study on clinical GBM tumors using multiple technologies to detect gene mutation, amplification, protein expression and promoter methylation. These data will inform planning for future personalized biomarker-based clinical trials and identifying effective treatments based on tumor biomarkers.

KEYWORDS:

EGFRvIII; IDH1; MGMT promoter methylation; glioblastoma; tumor profiling

PMID:
26933808
PMCID:
PMC5008305
DOI:
10.18632/oncotarget.7722
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center