Molecular Genetic and Clinical Characteristics of Glioblastoma with Oligodendroglial Component (GBM-O)
Christina L Appin, Candace S Chisolm, Cristina Vincentelli, Charlie Hao, Stephen B Hunter, Daniel J Brat. Emory University School of Medicine, Atlanta, GA
Background: Glioblastoma with oligodendroglial component, WHO grade IV (GBM-O) is a recently recognized subtype of GBM (WHO, 2007) with little known of its distinguishing clinical or molecular features. Common genetic alterations in classic GBM include EGFR amplification (amp, 40-50%), PTEN deletion (del, 80-90%), and MGMT promoter methylation (40-50%). Chromosome 1p and 19q co-deletion (co-del) is frequent in oligodendrogliomas (60-80%), but occurs in less than 5% of GBMs. Mutant IDH1 is present in 5-10% of primary GBMs and 70-80% of secondary GBMs. Here we describe molecular genetic and clinical features of GBM-O.
Design: Results of molecular testing on GBMs diagnosed from 2008 to 2011 at Emory University were analyzed. DNA methylation of the MGMT promoter was determined by methylation-specific PCR. EGFR, PTEN, 1p and 19q status were determined by fluorescence in situ hybridization (FISH). Immunohistochemistry was used to determine mutant IDH1 expression (IDH1R132H). Age at diagnosis and gender were also noted.
Results: Between 2008 and 2011, a total of 252 GBMs were diagnosed and 31 (12%) were classified as GBM-O. Patients with GBM-O were younger than those with classic GBMs (mean, 50.6 yrs vs. 58.6 yrs, respectively; Student's t test p = 0.04) and the majority were men (80% of GBM-O vs. 57% of classic GBM). MGMT promoter methylaton status was not substantially different between GBM-O and GBM (45% vs 50%, respectively). EGFR was amplified in 38% of classic GBMs compared to 26% of GBM-O. Almost all (95%) classic GBMs showed PTEN del compared to 75% of GBM-O. Co-del of 1p/19q was noted in 31% of GBM-O. Mutant IDH1 protein was detected in 31% of GBM-Os and 9% of classic GBMs.
Conclusions: GBM-O affects younger patients and a higher percentage of males than classic GBM. The spectrum of genetic alterations in GBM-O is slightly different than classic GBMs, with lower frequencies of EGFR amp and PTEN del and higher frequencies of 1p/19q co-del and IDH1 mutation.
Tuesday, March 20, 2012 1:00 PM
Platform Session: Section F, Tuesday Afternoon