SPECIFIC GENETIC PREDICTORS OF CHEMOTHERAPEUTIC RESPONSE AND SURVIVALIN PATIENTS WITH ANAPLASTIC OLIGODENDROGLIOMAS

Background/Methods: Gliomas are common malignant neoplasms of the cent ral nervous system, Among the major subtypes of gliomas, oligodendrogl iomas are distinguished by their remarkable sensitivity to chemotherap y, with approximately two thirds of anaplastic (malignant) oligodendro gliomas responding dramatically to combination treatment with procarba zine, lomustine, and vincristine (termed PCV). Unfortunately, no clini cal or pathologic feature of these tumors allows accurate prediction o f their response to chemotherapy. Anaplastic oligodendrogliomas also a re distinguished by a unique constellation of molecular genetic altera tions, including coincident loss of chromosomal arms 1p and 19q in 50% -70% of tumors. We have hypothesized that these or other specific gene tic changes might predict the response to chemotherapy and prognosis i n patients with anaplastic oligodendrogliomas, Therefore, we have anal yzed molecular genetic alterations involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and CDKN2A (on chromosome 9p) gen es, in addition to clinicopathologic features in 39 patients with anap lastic oligodendrogliomas for whom chemotherapeutic response and survi val could be assessed. Results/Conclusions: Allelic loss (or loss of h eterozygosity) of chromosome 1p is a statistically significant predict or of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitiv ity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both ch romosomes 1p and 19q were strongly associated with longer overall surv ival, whereas CDKN2A gene deletions and ring enhancement (i.e., contra st enhancement forming a rim around the tumor) on neuroimaging were as sociated with a significantly worse prognosis. The inverse relationshi p between CDKN2A gene deletions and losses of chromosomes Ip and 19q f urther implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These re sults suggest that molecular genetic analysis may aid therapeutic deci sions and predict outcome in patients with anaplastic oligodendrogliom as.