PATH-31 - Recurrent copy number changes in glioblastoma, IDH-wildtype: are other +7/-10 patterns clinically relevant?

Glioblastoma (GBM), IDH-wildtype (WT) is currently defined as an IDH-WT and H3-WT diffuse astrocytic glioma with molecular diagnostic features including whole +7/−10, TERT promoter (TERTp) mutation, and EGFR amplification and/or morphological diagnostic features such as necrosis and microvascular proliferation. To further understand the diversity of copy number signatures of GBM, IDHWT and evaluate the diagnostic utility of other recurrent copy number changes, we analyzed paired chromosomal microarray and next-generation sequencing mutational profiling data from 418 adult IDH-WT and H3-WT tumors with GBM morphological diagnostic features. The most common molecular features were TERTp mutations (85%), CDKN2A/B heterozygous/homozygous deletion (78%/66%), +7/-10 (63%), EGFR amplification (41%), +19 (36%), PTEN mutations (35%), partial -13 (33%), partial -14 (33%), +20 (32%), TP53 mutations (32%), and partial -22 (29%). At least one molecular diagnostic biomarker was present in 92% (n=385) of cases, and 29% (n=121) of cases had all three. The +7/-10 biomarker was the most frequent chromosomes 7/10 copy number change (68%, n=265). Other +7/-10 patterns were seen in 30% (n=125) of cases and included isolated +7 or -10, combinations of +7 and -10 with partial +7, partial -10 or 10 copy neutral loss of heterozygosity (cnLOH). Overall, 93% (390/418) of cases had whole and other chromosome 7/10 copy number changes. In comparison to tumors with +7/-10, tumors with other +7/-10 patterns were significantly enriched for partial 13 loss (Bonferroni adjusted p=0.04) but were not associated with significant difference in patient overall survival (p=0.30, 158/418 had available survival data).Our findings reiterate and expand the spectrum of copy number changes associated with GBM, IDH-WT. The similar overall survival rates between cases with the +7/-10 biomarker and those with other +7/-10 patterns suggest that other +7/-10 patterns may be functionally equivalent to +7/-10 and diagnostically relevant as a molecular diagnostic biomarker for this tumor type.