Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas

See the editorial by Jenkins, on pages 891–892. Diffuse gliomas are the most common intrinsic primary brain tumors in humans. World Health Organization criteria provide a scheme to segment the diffuse gliomas from low grade (II) through intermediate or anaplastic (grade III) to malignant (grade IV; also known as glioblastoma multiforme [GBM]). Grade II gliomas have a relatively favorable but highly variable prognosis. Patients with grade III lesions have a somewhat shorter but still variable survival. Those with GBM have the shortest lifespan with the least variability. There are several histological subtypes of low- and intermediate-grade gliomas, including the more common astrocytomas (AII, AIII), oligodendrogliomas (OII, OIII), mixed oligoastrocytomas (OAII, OAIII), and ependymomas (EII, EIII).1 Because prognosis is variable and response to therapy unclear, the management of patients who present with grade II–III gliomas is still controversial. The development of markers that reliably predict the behavior of these tumors would be useful both for counseling and for treatment planning of patients in this group.2 For some time, it has been recognized that malignant transformation of glial cells is associated with a number of genetic events, including p53 mutations, 1p/19q codeletion/translocation, loss of heterozygosity (LOH) of chromosomes 10 and 17p, as well as amplification of epidermal growth factor receptor (EGFR).3,4 Recently, mutations in the isocitrate dehydrogenase (IDH) genes 1 and 2 (IDH1 and IDH2) have been described in the majority of grade II–III astrocytomas and oligodendrogliomas, as well as in a minority of GBM.5–8 The most common IDH mutation occurring in gliomas is CGT to CAT at codon 132 in exon 4 of IDH1, resulting in an amino acid exchange from arginine to histidine (R132H). It has also been shown that patients whose grade III and grade IV gliomas carry IDH mutations have a better overall prognosis than patients whose gliomas are IDH-mutation negative.9–12 The impact of IDH mutation status (mIDH) on the prognosis of patients with grade II astrocytomas is not as clear. The present study was designed to test whether overall survival (OS) and progression free rate (PFR) of patients with clinically low-grade gliomas can be best predicted by pathological grading alone or a combination of molecular markers.