ALLELIC DELETION ANALYSES OF MMAC PTEN AND DMBT1 LOCI IN GLIOMAS - RELATIONSHIP TO PROGNOSTIC-SIGNIFICANCE/

The frequency of loss of heterozygosity (LOH) around MMAC/PTEN and DMB T1 loci and survival analyses based on the LOH status were assessed in 110 patients with different histological groups of gliomas. Twenty-si x of the patients had anaplastic oligodendrogliomas, 31 had anaplastic astrocytomas, and 53 had glioblastomas multiforme (GM). At the DMBT1 locus, LOH was observed very frequently in all three histological grou ps, with no significant difference in the frequency of LOH among the t hree histological groups. At the MMAC/PTEN locus, patients with GM exh ibited a significantly increased frequency of LOH (72%) compared with patients with anaplastic astrocytomas (29%) or anaplastic oligodendrog liomas (31%) (P < 0.0001). Kaplan-Meier survival plots showed that pat ients with LOH at the MMAC/PTEN locus had a significantly worse progno sis than did patients without LOH at the MMAC/PTEN locus [hazard ratio (LOH versus non-LOH), 2.65; 95% confidence interval (CI), 1.69-4.46; P < 0.0001]. Cox proportional hazards regression analysis, adjusted fo r age at surgery and histological grades (GM and non-GM), showed that LOH at the MMAC/PTEN locus was a significant predictor of shorter surv ival [hazard ratio (LOH versus non-LOH), 2.01; 95% CI, 1.1-3.5; P = 0. 018). Our analysis failed to indicate a similar association between th e frequency of LOH at the DMBT1 locus and patient survival [hazard rat io (LOH versus non-LOH), 2; 95% CI, 0.37-3.13; P = 0.2]. These results suggest that the DMBT1 gene may be involved early in the oncogenesis of gliomas, whereas alterations in the MMAC/PTEN gene may be a late ev ent in the oncogenesis related to progression of gliomas and provide a significant prognostic marker for patient survival.