Abstract A31: Association between TERT promoter mutations and BRAF/NRAS mutations in patients with primary and metastatic melanoma tumors

• DOI: 10.1158/1538-7445.mel2014-a31
• Publication Date: 2015-07-16T21:52:02Z
• Authors: Gregory A. Chang; Jyothirmayee S. T...; Nathaniel H. Fleming; Kevin Lui; Yongzhao Shao; Farbod Darvishian; Anna Pavlick; Russell Berman; Richard Shapiro; Iman Osman; David Polsky
• Keywords: V600E

Abstract Background: BRAF and NRAS are well-established driver oncogenes in melanoma. Mutations the promoter region of telomerase reverse transcriptase gene (TERT) increase expression have been identified at high rates metastatic melanoma, rarely familial One recent study found an association between TERT mutations or mutations. We developed mutation-specific assays to detect V600 Q61 along with C228T C250T identify prevalence these melanoma tumor samples, BRAF/NRAS mutations, potential use as a biomarker for blood-based monitoring. Methods: analyzed 316 primary tumors from 114 patients unresectable stage III/IV enrolled followed NYU Melanoma Biorepository program. Each patient had >1 samples available analysis. used combination allele-specific PCR (Taqman) SNaPshot V600E/K/R, Q61L/K/R patients. tested using Fisher's Exact Test. also plasma separate group 20 IV stable active disease time blood draw. Results: Among patients, 49, 40 22 2, 3 4 analysis respectively. There were whom we only 1 tumor. amplified 304/316 (96%) detected 177/304 (58%) tumors. 39/77 (51%) primaries 138/227 (61%) metastases. present 86/304 (28%) 87/304 (29%) >2 that 40/111 (36%) discordant (e.g. mutant wild-type). Six both either within different individual (n=2 patients) same (n=4 patients). 307/316 (97%) samples. 95/307 (31%) V600E/K/R 22/77 73/227 (32%) 54/307 (18%) Q61K/L/R 7/77 (9%) 47/227 (21%) 177 72/177 (41%) 34/177 (19%). was statistically significant occurrence (OR=4.32, p<0.01, 95% CI 1.57-11.91) (OR=3.16, 1.79-5.56). Overall, 21/74 85/222 (38%) metastases NRAS. On per-patient basis, 64/114 (56%) least NRAS-mutant BRAF-mutant tumor; 86/114 (75%) 98/114 (86%) mutation mutation. 1/20 (5%) sample. Conclusions: C228T/C250T occur more frequently than melanomas. preferentially associated suggesting possible cooperative role oncogenes. The frequency on basis combined presence inter-tumor heterogeneity detection mutated DNA suggest may be useful large proportion Citation Format: Gregory A. Chang, Jyothirmayee S. Tadepalli, Nathaniel H. Fleming, Kevin Lui, Yongzhao Shao, Farbod Darvishian, Anna Pavlick, Russell Berman, Richard Shapiro, Iman Osman, David Polsky. Association [abstract]. In: Proceedings AACR Special Conference Advances Melanoma: From Biology Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A31.