by Michael D. O’Neill, Editor & Publisher, BioQuick News
Scientists at Tempus AI, a Chicago-based company dedicated to AI-enabled precision medicine, have identified somatic mutations and tumor gene expression differences associated with genetic ancestry in a study of colorectal cancer (CRC). The work was published August 13, 2024 in Genome Medicine, and the open-access article is titled “Association of Genetic Ancestry with Molecular Tumor Profiles in Colorectal Cancer.” According to the Methods section, “Sequencing was performed with the Tempus xT NGS 648-gene panel and whole exome capture RNA-Seq for 8,454 primarily late-stage CRC patients. Genetic ancestry proportions for five continental groups—Africa (AFR), American indigenous (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS)—were estimated using ancestry informative markers. Most results (but not all) were replicated by analyzing imputed race and ethnicity. The research team assessed association of genetic ancestry proportions with somatic mutations in relevant CRC genes and in 2,608 expression profiles, as well as 1,957 CRC consensus molecular subtypes (CMS).
The scientists found that increased AFR ancestry was associated with higher odds of somatic mutations in the cancer-related genes APC, KRAS, and PIK3CA and lower odds of mutations in the BRAF proto-oncogene. Additionally, increased EAS genetic ancestry was associated with lower odds of mutations in KRAS, EUR with higher odds in BRAF, and the Hispanic/Latino category with lower odds in BRAF. Greater AFR ancestry and the Non-Hispanic (NH) Black category were associated with higher rates of consensus molecular subtype 3 (CMS3), while a higher proportion of Hispanic/Latino patients exhibited indeterminate CMS classifications.
Conclusion
In their Conclusion, the authors wrote: “Molecular differences in CRC tumor mutation frequencies and gene expression that may underlie observed differences by race and ethnicity were identified. The association of AFR ancestry with increased KRAS mutations aligns with higher CMS3 subtype rates in NH Black patients. The increase of indeterminate CMS in Hispanic/Latino patients suggests that subtype classification methods could benefit from enhanced patient diversity.”
Comments from Co-Corresponding Author
Co-corresponding author Francisco De La Vega, PhD, (formerly with Tempus AI, and presently an Adjunct Professor in the Department of Biomedical Data Science, Stanford University School of Medicine) had the following to say about the newly published work:
“This study explores how genetic ancestry influences tumor profiles in CRC, using new methodological advances to shed light on the molecular changes underlying disparities in CRC outcomes across different racial and ethnic groups. By analyzing genomic profiles and clinical data from de-identified records of over 8,400 late-stage CRC patients from the Tempus AI database, we identified associations between genetic ancestry and patterns of somatic mutation and gene expression.”
“For example, we found that individuals with higher African ancestry have increased odds of mutations in key cancer genes like KRAS, while those with East Asian ancestry showed lower odds for the same mutations. Our research also highlights that current methods for cancer subtype classification might benefit from including more diverse patient populations during development.”
“This work underscores the importance of considering genetic ancestry in understanding and addressing racial and ethnic health disparities in cancer outcomes.”
The other co-corresponding author of the Genome Biology article is Nina N. Sanford, MD, Chief of Gastrointestinal Radiation Oncology Service, Department of Radiation Oncology, University of Texas Southwestern (UTSW) Medical Center.