Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers Journal Article
| Authors: | Jiagge, E.; Jin, D. X.; Newberg, J. Y.; Perea-Chamblee, T.; Pekala, K. R.; Fong, C.; Waters, M.; Ma, D.; Dei-Adomakoh, Y.; Erb, G.; Arora, K. S.; Maund, S. L.; Njiraini, N.; Ntekim, A.; Kim, S.; Bai, X.; Thomas, M.; van Eeden, R.; Hegde, P.; Jee, J.; Chakravarty, D.; Schultz, N.; Berger, M. F.; Frampton, G. M.; Sokol, E. S.; Carrot-Zhang, J. |
| Article Title: | Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers |
| Abstract: | Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery. © 2023 The Authors |
| Keywords: | controlled study; gene mutation; gene sequence; major clinical study; sequence analysis; genetics; mutation; proto-oncogene proteins; united states; cancer patient; pancreas cancer; colorectal cancer; biological marker; breast cancer; protein depletion; lung neoplasms; prevalence; epidermal growth factor receptor; cohort analysis; lung cancer; smoking; pathology; validation study; protein tyrosine kinase; protein p53; prostate cancer; lung tumor; gene fusion; protein-tyrosine kinases; k ras protein; medical care; tumor gene; protein p21; proto-oncogene proteins p21(ras); race difference; b raf kinase; oncogene myc; african; ccne1 gene; non-smoker; next-generation sequencing; ros1 gene; humans; human; male; article; precision oncology; oncogenomics; malignant neoplasm; real-world data; african ancestry; proto oncogene protein; driver alteration |
| Journal Title: | Cancer Cell |
| Volume: | 41 |
| Issue: | 11 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2023-11-13 |
| Start Page: | 1963 |
| End Page: | 1971.e3 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2023.10.003 |
| PUBMED: | 37890492 |
| PROVIDER: | scopus |
| PMCID: | PMC11097212 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Corresponding author is MSK author: Jian Carrot-Zhang -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work