GENO-22TWO DNA TESTS ACCURATELY CLASSIFY GLIOMAS INTO FIVE MOLECULAR GROUPS AND PROVIDE ADDITIONAL INFORMATION ON ACQUIRED ALTERATIONS

BACKGROUND: It has recently been shown that adult gliomas can be categorized into five molecular groups based on IDH mutation, 1p/19q codeletion and TERT promoter mutation (Eckel-Passow et al. N Engl J Med 2015 Epub Jun 10). We developed two genomics tests to assess these alterations and the other acquired alterations that are associated with the five glioma molecular groups. METHODS: DNA was isolated from 137 formalin-fixed, paraffin-embedded (FFPE) Mayo Clinic adult gliomas. First, copy number variants (CNV) and copy neutral loss of heterozygosity (cnLOH) were evaluated using the OncoScan platform (Affymetrix). Second, 50 genes commonly mutated in brain tumors – including TERT and IDH - were evaluated by multiplex PCR and pooled next-generation sequencing. The 50-gene panel included TP53 and ATRX. RESULTS: Together, the OncoScan CNV/cnLOH array and the 50-gene panel classified 135 (99%) of the gliomas into one of the five molecular groups: 29 (21%) Triple-Positive; 6 (4%) TERT- and IDH-mutation; 36 (26%) IDH-mutation only; 2 (1%) Triple-Negative; and 62 (45%) TERT-mutation only. Two (1%) had other patterns. Interesting findings included: Among the IDH-mutation only gliomas, all (100%) acquired a TP53 alteration and 31 (86%) an ATRX alteration. CnLOH of 17p (including TP53) was observed in 22 gliomas; 19 were IDH-mutation only. Acquired TP53 alterations were observed in all 22 tumors with 17p cnLOH. While most tumors were either TERT or ATRX mutated, some had mutations in both genes and some in neither. CIC and/or FUBP1 mutations were detected in 21 (72%) of the Triple-Positive gliomas. CnLOH of 9p was observed in 4 (14%) Triple-Positive gliomas. CONCLUSIONS: Two genomics tests using FFPE material can effectively classify gliomas into one of five molecular groups. The tests also identify common acquired alterations associated with these groups. These tests will be a significant adjunct to the clinical diagnosis of adult gliomas.