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Observational Study
. 2024 Jan 5;29(1):8-14.
doi: 10.1093/oncolo/oyad208.

TERT Promoter Mutations Frequency Across Race, Sex, and Cancer Type

Talal El Zarif  1   2   3 , Marc Machaalani  4 , Rashad Nawfal  4 , Amin H Nassar  5 , Wanling Xie  6 , Toni K Choueiri  1   2 , Mark Pomerantz  1   2
Affiliations
Observational Study

TERT Promoter Mutations Frequency Across Race, Sex, and Cancer Type

Talal El Zarif et al. Oncologist. .

Abstract

Background: Telomerase reverse transcriptase (TERT) gene promoter mutations have been explored, as biomarkers of improved survival for patients with cancer receiving immune checkpoint inhibitors. We sought to investigate their prevalence by race and sex across different cancer types to inform patient selection in clinical trials.

Results: In this observational study, 31 925 patients with cancer underwent next-generation sequencing of their tumors with 88% (27 970) patients self-reported being Whites, 7.1% (2273) Asians, and 5.3% (1682) Blacks. Examining the distribution of TERT promoter mutations by race, White patients with melanoma harbored more TERT promoter mutations than Asian and Black patients (OR = 25.83; 95%CI, 6.84-217.42; P < .001). In contrast, Asian patients with head and neck cancer (HNC) harbored more TERT promoter mutations compared to White patients (OR = 2.47; 95%CI, 1.39-4.37; P = .004). In addition, the distribution of TERT promoter mutations differed by sex. Males were enriched for TERT gene promoter mutations compared to females with melanoma (OR = 1.82; 95%CI, 1.53-2.16; P < .001), cancer of unknown primary (OR = 1.96; 95%CI, 1.43-2.69; P < .001), hepatobiliary (OR = 3.89; 95%CI, 2.65-5.69; P < .001), and thyroid cancers (OR = 1.42; 95%CI, 1.10-1.84; P = .0087), while females were more enriched for TERT promoter mutations compared to males for HNC (OR = 0.56; 95%CI, 0.39-0.81; P = .0021).

Conclusions: The prevalence of TERT gene promoter mutations varies among patients with cancer based on race and sex. These findings inform our understanding of cancer biology and can assist in the design of future clinical trials that leverage drugs targeting TERT promoter dependencies.

Keywords: TERT mutation; disparities in cancer care; immune checkpoint inhibitor.

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Conflict of interest statement

T.E.Z. received honoraria from art tempi for work unrelated to this work. W.X. serves as consultant for Convergent Therapeutics, Inc. T.K.C. reports institutional and/or personal, paid and/or unpaid support for research, advisory boards, consultancy, and honoraria from Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, and others), outside the submitted work. Institutional patents filed on molecular alterations and immunotherapy response/toxicity, and ctDNA. Equity: Tempest, Pionyr, Osel, Precede Bio, CureResponse. Committees: NCCN, GU Steering Committee, ASCO/ESMO, ACCRU, KidneyCan. Medical writing and editorial assistance support may have been funded by Communications companies in part. No speaker’s bureau. Mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components. The institution (Dana-Farber Cancer Institute) may have received additional independent funding of drug companies or/and royalties potentially involved in research around the subject matter. T.K.C. is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus Fund, and Loker Pinard Funds for Kidney Cancer Research at DFCI. The other authors indicated no financial relationships.

Figures

Figure 1.
Figure 1.
The distribution of TERT promoter mutations across the top 10 cancer types.
Figure 2.
Figure 2.
The frequency of TERT promoter mutations in solid tumors among males compared to females. Abbreviations: OR: Odds ratio; 95%CI: 95% confidence interval; *Q-value < 005; **Q-value < .01; ***Q-value < .001.
Figure 3.
Figure 3.
The frequency of TERT promoter mutations in different subgroups across cancer types.
See this image and copyright information in PMC

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