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A catalogue of missense and nonsense mutation abundances for the U.S. cancer patient population

Arun, A.; Liarakos, D.; Mendiratta, G.; McFall, T.; Hargreaves, D. C.; Wahl, G. M.; Hu, J.; Stites, E. C.

2026-04-22 oncology
10.64898/2026.04.20.26351248 medRxiv
Show abstract

Widespread genomic sequencing efforts have characterized the molecular foundations of the different cancers. By combining these genomic data in a manner proportional to the population-level abundances of these different cancers, we estimate the overall abundances of each observed missense and nonsense mutation within the U.S. cancer patient population. We find BRAF V600E (5.2%) is the most common mutation in the cancer patient population, TP53 R175H (1.5%) is the most common tumor suppressor mutation, and APC R876X (0.4%) is the most common nonsense mutation. These values differ largely and significantly from what would be found in a typical pan-cancer analysis, where different cancer types are included out of proportion to population level incidence. We present the full ordered lists of population-level abundances for specific missense and nonsense mutations, and we demonstrate the value of these data by further analyzing high priority genes (e.g., TP53, KRAS, BRAF) and pathways (e.g., RTK/RAS, PI3K, and WNT/{beta}-catenin). Overall, this information is a resource that should benefit the basic science, translational, and clinical cancer research communities.

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