Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis.

TLDR

Prior work showed that loss of chromosome 1p in anaplastic oligodendrogliomas was linked to better chemotherapeutic response and overall survival, yet it failed to identify all chemosensitive tumors or predict long survival. The study sought to determine the clinical value of molecular genetic testing at diagnosis by evaluating a homogeneous cohort of 50 patients with anaplastic oligodendroglioma treated primarily with chemotherapy. The authors performed molecular genetic analyses on 50 histologically confirmed anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. Four genetically defined subgroups emerged: tumors with isolated 1p/19q loss showed durable responses and long survival; tumors with other 1p alterations responded briefly; TP53‑mutated 1p‑negative tumors recurred quickly; and TP53‑negative 1p‑negative tumors were aggressive, poorly responsive, and clinically similar to glioblastomas, indicating that therapy could be tailored at diagnosis.

Abstract

In a prior study of anaplastic oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival. To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma.