DYNAMICS OF GENETIC ALTERATIONS ASSOCIATED WITH GLIOMA RECURRENCE

We investigated the dynamics of the generic changes that are associate d with two types of glioma recurrence, that is, progression from a low er-grade to a high-grade tumor (7 cases) and development of a same hig h-grade recurrence (15 cases). Each pair of tumors was analyzed for TP 53 mutation, EGFR amplification, and loss of heterozygosity for tumor suppressor genes (TP53, RE I, CDKN2A, PTEN, DMBT1) and tumor suppresso r gene regions (1p36, 19q13, 11p15, 10p15) known to be frequently impl icated in glioma tumorigenesis. By comparing the genetic changes in th e primary and corresponding secondary tumors, we found that additional loss of CDKN2A and/or RBI, encoding important components of the cell cycle regulatory pathway, was the most frequent genetic change in both types of recurrence development (10 of 22 cases, 45%). Additional los s of heterozygosity for the 10p15 region, for PTEN, and/or for DMBT1 i n the recurrent tumor was noted in 7 of 22 cases (32%), suggesting tha t additional inactivation of tumor suppressor genes on chromosome IO i s another important feature of glioma relapse. Less frequent additiona l losses were detected for chromosome regions 11p15 and 19q13 (3 of 22 cases, 14%, each). We conclude that glioma recurrences are characteri zed by an increased involvement of tumor suppressor genes, even in tho se cases in which the primary and secondary tumor are of the same high malignancy grade. (C) 1998 Wiley-Liss, Inc.