Characterizing telomerase reverse transcriptase (TERT) promoter mutations (mut) across sex, race, and cancer types.

Abstract

3122 Background: TERT promoter mut. have been evaluated as a predictive biomarker for patients (pts) receiving immune checkpoint inhibitors. Understanding the prevalence of TERT promoter mut. by sex, race, and cancer type is essential for optimizing its use. Methods: Pts who underwent next-generation sequencing at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center were identified from the AACR Genomics Evidence Neoplasia Information Exchange (GENIE) registry v11.0. Self-reported race and sex data were extracted for ten cancer types with the highest prevalence of TERT promoter mut. The strength of associations with TERT promoter mut. was quantified by Odds ratios (ORs) and two-sided Fisher’s exact tests, along with FDR-adjusted q-values using the Benjamini-Hochberg method. Results: We identified 31,925 pts – 87.6% (27,970) self-identified as White, 7.1% (2,273) Asian, and 5.3% (1,682) Black. TERT promoter mut. were present in 17% (5,470) tumors, including 56% (1,346/2,411) bladder cancers, 43% (966/2,243) melanomas, 41% (395/959) thyroid cancers, and 23% (183/782) head and neck cancers (HNC). TERT promoter mut. were significantly higher in males vs. females in melanoma, cancer of unknown primary (CUP), hepatobiliary (HPB), and thyroid cancers. In contrast, males harbored fewer mut. vs. females with HNC. Interestingly, TERT promoter mut. varied by race. Mut. frequency was significantly higher in White pts with melanoma (44%, n=964/2176) compared to Asian and Black pts (2.9%, n= 2/67) (OR=25.8; 95% CI = 6.9 - 217, p<0.0001). Asian males with HNC (37%, n= 22/60) were enriched for TERT promoter mut. vs. White males (19%, n= 93/489) (OR = 2.5; 95% CI = 1.4 - 4.4; q=0.03). Within HNC tumors, oral cavity (OC) tumors (44.3%, n= 85/192) were associated with higher TERT promoter mut. vs. other HNC subtypes (16.6%, n= 98/590) (OR = 4.4; 95% CI = 3.03 - 6.26; p<0.0001). Asian pts with OC (70%, n=14/20) harbored more mut. vs. White pts with OC (41.4%, n=70/169) (OR = 3.3; 95% CI = 1.2 - 9; p<0.05). Conclusions: Our study demonstrates differences in the distribution of TERT promoter mut. by sex, race, and cancer type. Considering these variations is crucial for future clinical trial design and biomarker studies. [Table: see text]