Gene Variation Predicts Survival in Brain Cancer Patients

Qingyi Wei, MD, Ph.D.
University of Texas M.D. Anderson Cancer Center
R01ES1174

Background: Glioblastoma multiforme (GBM) is the most aggressive of a form of central nervous system tumor known as glioma. Gliomas, as their name implies, arise from glial cells; cells that provide protection for neurons in the central nervous and supply them with nutrients. The cause of GBM is not known. GBM accounts for over half of all primary brain tumor cases. The development of biomarkers for GBM could be useful to modify treatments and improve outcomes of patients with GBM.

One such biomarker is the expression of human telomerase (hTERT), an enzyme that adds specific DNA sequence repeats to the ends of DNA strands in the telomere regions of the chromosomes. The level of hTERT expression has been shown to be a good outcome predictor for many cancers including cancer of the lung, breast, cervix, stomach, and colon.

Advance: A team of researchers supported by NIEHS and NCI at the M.D. Anderson Cancer Center in Houston, Texas has recently discovered a genetic variation in the hTERT gene that is predictive of survival outcome of GBM patients. In previous research, the team found variations, or alleles, of the gene. These alleles were deemed either short (S) or long (L) based on the length of the DNA sequences. In the current study, median survival for patients with two short alleles (SS genotype) was about 11 months longer than those with either one or two long alleles (SL or LL genotypes).

Implications: This study is important because it shows that molecular differences that relate to gene length can be predictive of treatment outcome. It also adds to the body of information suggesting that hTERT is a possible target for therapeutic agents to combat cancer. The researchers caution that larger studies are necessary to verify these findings.

Citation: Wang L, Wei Q, Wang LE, Aldape KD, Cao Y, Okcu MF, Hess KR, El-Zein R, Gilbert MR, Woo SY, Prabhu SS, Fuller GN, Bondy ML. Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation. J Clin Oncol. 2006 Apr 1;24(10):1627-32.