+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Genetic variations in EGF and EGFR and glioblastoma outcome



Genetic variations in EGF and EGFR and glioblastoma outcome



Neuro-Oncology 12(8): 815-821



Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94-1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99-1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.

(PDF emailed within 0-6 h: $19.90)

Accession: 053389538

Download citation: RISBibTeXText

PMID: 20197289

DOI: 10.1093/neuonc/noq018


Related references

Genetic variations in VEGF and VEGFR2 and glioblastoma outcome. Journal of Neuro-Oncology 104(2): 523-527, 2011

Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab. International Journal of Oncology 41(3): 1029-1035, 2013

High-throughput screening identified inherited genetic variations in the EGFR pathway contributing to skin toxicity of EGFR inhibitors. Pharmacogenomics 16(14): 1605-1619, 2016

Screening for EGFR amplifications with a novel method and their significance for the outcome of glioblastoma patients. Plos One 8(6): E65444-E65444, 2014

Whole genome sequencing of glioblastoma multiforme identifies multiple structural variations involved in EGFR activation. Mutagenesis 29(5): 341-350, 2015

PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. Journal of the National Cancer Institute 93(16): 1246-1256, 2001

EGFR as a genetic therapy target for glioblastoma and mammary carcinoma radiosensitization. Proceedings of the American Association for Cancer Research Annual Meeting 42: 715, March, 2001

Correlation of molecular genetic analysis of p53, MDM2, p16, PTEN, and EGFR and survival of patients with anaplastic astrocytoma and glioblastoma. Frontiers in Bioscience 8: E281-E288, 2003

The infrequent simultaneous genetic alterations in glioblastoma multiforme (LOH 10, 17,19q, TP53 mutation and EGFR amplification) with short clinical course. Polish Journal of Pathology 58(2): 79-85, 2007

Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth. Journal of Clinical Investigation 123(6): 2475-2487, 2013

EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy. Oncology Reports 31(1): 480-487, 2014

Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR. Journal of Experimental & Clinical Cancer Research 31(): 65-65, 2013

Phosphorylated EGFR expression may predicts outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR. 2012

A urokinase receptor-Bim signaling axis emerges during EGFR inhibitor resistance in mutant EGFR glioblastoma. Cancer Research 75(2): 394-404, 2015