Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors

Recent studies have revealed a correlation between specific genetic changes, such as loss of chromosome 1p and 19q, and sensitivity of oligodendroglial neoplasm to radiotherapy and chemotherapy; epigenetic changes also play an important role in some tumors. In this retrospective study, we analyzed chromosomal alterations in 17 loci and promoter methylation status of 8 tumor‐related genes in 49 oligodendroglial tumors (29 WHO grade II and 11 WHO grade III oligodendrogliomas; 7 WHO grade II and 2 WHO grade III oligoastrocytomas) using quantitative microsatellite analysis and methylation‐specific polymerase chain reaction and correlated this information with clinical data. We also performed immunohistochemical stains for Ki‐67 and O (6)‐methyl guanine‐DNA methyl transferase. Our results showed that the frequency of deletions in regions on 1p, 9p, 10q, 17p and 19q were 71.4%, 26.5%, 6.1%, 69.4% and 89.8%, respectively. Promoter methylation was detected in p14, p15, p16, p53, p73, PTEN, MGMT and RASSF1A genes in 24.5%, 6.1%, 46.9%, 0%, 6.1%, 42.9%, 53.1% and 77.6% of tumors, respectively. Statistical analysis identified that 9p22 loss, p73 methylation and p15 methylation were independently associated with reduced overall survival, and Ki‐67 labeling index (LI) ≥ 5%, 9p22 loss, no loss of 19q, p73 methylation, p14 methylation and unmethylated MGMT predicted shorter progression‐free survival. Our findings suggest that the frequent deletion and hypermethylation of tumor‐related genes may represent a mechanism of tumor development and progression and emphasize the importance of defining new molecular markers for predicting prognosis, tumor recurrence and therapeutic response in cancer management. © 2009 UICC