PATH-37. <i>MTAP</i> Loss in Serial Samples in Patients with Glioblastoma, IDH Wild-Type

Abstract BACKGROUND The MTAP gene is located next to CDKN2A in chromosomal region 9p21. MTAP is homozygously deleted in approximately half of patients with glioblastoma, IDH wild-type, and are thought to be clonal genetic alterations that may be targetable with PRMT5 and MAT2A inhibitors. Method: 621 samples from 538 patients were sequenced with the next-generation sequencing platform, MSK IMPACT 505, and the status of MTAP, CDKN2A, and EGFR were interrogated. RESULTS 267/538 (50%) patients had MTAP copy number loss; of these, 265/267 (99%) patients had concurrent copy number loss of CDKN2A. 53/267 (20%) of patients with MTAP alterations had multiple sequenced samples: 42/53 (79%) patients had copy number loss of MTAP on the first sequenced sample, while 11/53 (21%) patients acquired the copy number loss on the subsequent sample. Of the 42 patients with MTAP copy number loss on the first sequenced sample, 7 patients were excluded due to low tumor content/low sequencing depth on the subsequent sample. 33/35 (94%) patients retained the alteration whereas 2/35 (6%) patients lost the alteration in conjunction with loss of CDKN2A. EGFR amplification was identified in 257 (48%) patients of the 538 patient cohort. Of these, 54/257 (24%) patients had EGFR amplification on the first sample and had an additional sample with adequate tumor content/sequencing depth; 51/54 (94%) patients retained the alteration, and 3/54 (6%) patients lost the alteration. CONCLUSIONS MTAP copy number loss are common alterations, which occur in conjunction with CDKN2A copy number loss, which can be acquired later in the tumor’s natural history and is retained on serial resections at a rate similar to EGFR amplification.