Supplementary Figure from Genetic Ancestry Correlates with Somatic Differences in a Real-World Clinical Cancer Sequencing Cohort

Arora, Kanika; Tran, Thinh N.; Kemel, Yelena; Mehine, Miika; Liu, Ying L.; Nandakumar, Subhiksha; Smith, Shaleigh A.; Brannon, A. Rose; Ostrovnaya, Irina; Stopsack, Konrad H.; Razavi, Pedram; Safonov, Anton; Rizvi, Hira A.; Hellmann, Matthew D.; Vijai, Joseph; Reynolds, Thomas C.; Fagin, James A.; Carrot-Zhang, Jian; Offit, Kenneth; Solit, David B.; Ladanyi, Marc; Schultz, Nikolaus; Zehir, Ahmet; Brown, Carol L.; Stadler, Zsofia K.; Chakravarty, Debyani; Bandlamudi, Chaitanya; Berger, Michael F.

doi:10.1158/2159-8290.22542027.v1

Supplementary Figure from Genetic Ancestry Correlates with Somatic Differences in a Real-World Clinical Cancer Sequencing Cohort

journal contribution

posted on 2023-04-04, 00:23 authored by Kanika Arora, Thinh N. Tran, Yelena Kemel, Miika Mehine, Ying L. Liu, Subhiksha Nandakumar, Shaleigh A. Smith, A. Rose Brannon, Irina Ostrovnaya, Konrad H. Stopsack, Pedram Razavi, Anton Safonov, Hira A. Rizvi, Matthew D. Hellmann, Joseph Vijai, Thomas C. Reynolds, James A. Fagin, Jian Carrot-Zhang, Kenneth Offit, David B. Solit, Marc Ladanyi, Nikolaus Schultz, Ahmet Zehir, Carol L. Brown, Zsofia K. Stadler, Debyani Chakravarty, Chaitanya Bandlamudi, Michael F. Berger

Supplementary Figure from Genetic Ancestry Correlates with Somatic Differences in a Real-World Clinical Cancer Sequencing Cohort

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

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ARTICLE ABSTRACT

Accurate ancestry inference is critical for identifying genetic contributors of cancer disparities among populations. Although methods to infer genetic ancestry have historically relied upon genome-wide markers, the adaptation to targeted clinical sequencing panels presents an opportunity to incorporate ancestry inference into routine diagnostic workflows. We show that global ancestral contributions and admixture of continental populations can be quantitatively inferred using markers captured by the MSK-IMPACT clinical panel. In a pan-cancer cohort of 45,157 patients, we observed differences by ancestry in the frequency of somatic alterations, recapitulating known associations and revealing novel associations. Despite the comparable overall prevalence of driver alterations by ancestry group, the proportion of patients with clinically actionable alterations was lower for African (30%) compared with European (33%) ancestry. Although this result is largely explained by population-specific cancer subtype differences, it reveals an inequity in the degree to which different populations are served by existing precision oncology interventions. We performed a comprehensive analysis of ancestral associations with somatic mutations in a real-world pan-cancer cohort, including >5,000 non-European individuals. Using an FDA-authorized tumor sequencing panel and an FDA-recognized oncology knowledge base, we detected differences in the prevalence of clinically actionable alterations, potentially contributing to health care disparities affecting underrepresented populations.This article is highlighted in the In This Issue feature, p. 2483