Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation.
OBJECTIVE
Glioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT mRNA expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients.


METHODS
We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and determined hTERT genotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables.


RESULTS
Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome.


CONCLUSIONS
A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.
Wang
Luo
L
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1439, USA.
Wei
Qingyi
Q
Wang
Li-E
LE
Aldape
Kenneth D
KD
Cao
Yumei
Y
Okcu
M Fatih
MF
Hess
Kenneth R
KR
El-Zein
Randa
R
Gilbert
Mark R
MR
Woo
Shiao Y
SY
Prabhu
Sujit S
SS
Fuller
Greg N
GN
Bondy
Melissa L
ML
D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D019098:Telomerase / Q000235:genetics*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase