[488] Next Generation Sequencing of a Large Cohort of Solid Tumors Reveals IDH1 Mutations Present in Melanoma at a Higher Frequency Than Expected

Bryce P Portier, Keyur P Patel, Rajesh Singh, Mark Routbort, Brian Handal, Bedia A Barkoh, Neelima Reddy, Alex Lazar, Michael Davies, L Jeffrey Medeiros, Ken Aldape, Rajyalakshmi Luthra. MD Anderson, Houston, TX

Background: Systematic genome sequencing has revealed that IDH1 (R132C) mutations are frequent and provide important prognostic information in glioblastomas. In addition, IDH1 mutations are observed in approximately 10% of cytogenetically normal acute myeloid leukemia cases and are associated with a specific clinicopathologic profile. The prevalence of IDH1 mutation in solid tumors, especially melanomas, is not well established. In this study, we screened for the presence of IDH1 mutations in a large cohort of sequentially tested solid tumors utilizing Next Generation Sequencing (NGS).
Design: A total of 910 solid tumor cases were sequentially screened for mutations utilizing a 46-gene NGS AmpliSeq™ Cancer Panel (Life Technologies, CA, USA). The study group included solid tumors of various types as well as both primary and metastatic tumors. In particular, the study included 208 melanomas and 702 other solid tumors.
Results: Mutations in IDH1 were detected in a total of 14 (1.5%) solid tumors. Specifically, IDH1 mutation R132C was observed in 10 melanomas representing 4.8% of all melanomas (1.1% of all tumors tested). IDH1 mutations were also detected in 4 non-melanocytic solid tumors (lung adenocarcinoma (n=2; R132S and R132L), colonic adenocarcinoma (n=1; R132C), and an undifferentiated carcinoma of unknown primary (n=1; R132C)). In melanomas, IDH1 co-mutations included BRAF, EGFR, TP53, CTNNB1, KDR, NRAS, and MLH1 with BRAF co-mutation in 75% of cases. In non-melanocytic solid tumors, IDH1 co-mutations included KRAS, NRAS, TP53, and GNAS with KRAS co-mutation in 100% of cases.
Conclusions: High throughput NGS is a useful tool for detecting IDH1 mutations and determining their frequency in solid tumors. Using this strategy, we show that IDH1 mutations are present in approximately 5% of melanomas, a frequency greater than that suggested in earlier studies. Additional mutations are frequently seen in conjunction with IDH1 mutation. The most frequent co-mutations in this cohort were BRAF in melanomas and KRAS in non-melanocytic carcinomas.
Category: Dermatopathology

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 42, Tuesday Morning


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