O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and relation to 1p/19q loss in low grade gliomas: A GICNO study

Abstract

20064 Background: 1p and 19q deletions have been associated with a favorable response to chemotherapy and a good prognosis in patients (pts) with oligodendroglioma. MGMT promoter methylation has been associated with a longer survival in pts with glioblastoma who receive alkylating agents. As yet, there are no data on the expression of MGMT, and on the relationship between 1p/19q deletions and MGMT promoter methylation in low grade glioma (LGG). Methods: Pts that received a first line chemotherapy regimen with temozolomide for progressive LGG were enrolled in the study, designed to investigate the correlation between MGMT methylation status and 1p/19q deletions in this setting. 1p/19q deletions were analysed by FISH, and MGMT promoter methylation by methylation specific PCR (MSP). Results: Seventy-five pts (26 females, 49 males; median age 42 years: range 22–68 years) were accrued. Of these, 48 (64%) had oligodendrogliomas (O), 19 (25.3%) astrocytomas (A), and 8 (10.6%) oligoastrocytomas (OA); 44 (58.7%) had a history of epilepsy, 41 (54.7%) had a frontal tumor localization, 27 (36%) had MRI contrast enhancing lesions, and 35 (46.7%) had been pre-treated with radiotherapy. 1p/19q deletions, evaluable in 58 pts (77.3%), were both present in 36 pts (62%), (3 being A and 2 OA); 18 pts (31%) had no loss; 1 pt (1.7%) had 1p loss; 3 pts (5.2%) 19q loss. Combined 1p and 19q loss was not correlated with a frontal localization (p = 0.12), median age (0.47) and/or gender (0.62). MGMT promoter methylation, present in 17 (56.6%) of 30 assessable cases, was significantly associated with combined 1p/19q deletions (p = 0.03). MGMT promoter methylation was not significantly associated with age (p = 0.46), gender (p = 0.2), tumor localization (p = 0.12) and/or histology (0.37). Conclusions: 1p/19q deletions are strictly correlated to histology and to MGMT promoter methylation; further prospective trials are required to clarify the impact of these molecular signatures on clinical outcome. No significant financial relationships to disclose.