Molecular subtypes of anaplastic oligodendroglioma: Implications for patient management at diagnosis

Purpose: In a prior study of anaplastic oligodendrogliomas treated with che motherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome Ip correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic managemen t was not uniform, loss of Ip did not identify all chemosensitive tumors, n or did all patients whose tumors harbor a Ip loss have long survival. Experimental Design: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrog liomas, we studied a larger, more homogeneous group of 50 patients with his tologically defined anaplastic oligodendrogliomas treated with a chemothera peutic regimen as the principal initial therapy, Results: We demonstrate that these tumors can be divided genetically into f our therapeutically and prognostically relevant subgroups. Patients whose t umors have combined but isolated losses of Ip and 19q have marked and durab le responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome Ip alteratio ns also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking Ip loss can also be divided into two subgr oups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsi ve, aggressive tumors that are clinically and genotypically similar to glio blastomas. Conclusions: These data raise the possibility, for the first time, that the rapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma.