IKCS 2022: Genetic Ancestry and Molecular Correlations in Patients with Kidney Cancers

(UroToday.com) Dr. Ritesh Kotecha presented his work to characterize the distribution of clinical and genomic factors between germline-defined ancestral genetic groups. Genetic ancestry refers to the genomic differences which characterize ancestral populations, commonly categorized as: European, African, South Asian, East Asian, and Native American. Previous studies demonstrated enrichment of VHL, PBRM1, CHEK2, and 3p loss among patients of European relative to African ancestry and enrichment of FH in patients of African relative to European ancestry.

Dr. Kotecha performed a single-institution (MSKCC) retrospective analysis of RCC patients and examined for correlations with germline genetic data as determined from paired tumor-normal germline/somatic tumor mutational profiling (MSK IMPACT). Over 950 RCC patients were analyzed (78% European, 12% Admixed, 5% African).


Germline genetic results correlated very well with self-reported racial ancestry.


Patients of African ancestry in the MSKCC cohort were more likely to have presented with metastatic disease, and less likely to have favorable risk disease (0% versus 31% among patients of African versus European ancestry). Notably, clear cell histology was most common among the cohort overall, but the African ancestral group was enriched for rare histologies, especially papillary RCC (30% versus 9% among patients of African versus European ancestry).

The most common germline alterations among the overall cohort were CHEK2 and FH. While the European ancestral cohort was enriched for CHEK2 alterations, the African ancestral cohort was enriched for FH alterations.


Examining the somatic mutational landscape specifically in the clear cell cohort, Dr. Kotecha identified lower rates of somatic VHL and PBRM1 mutation and a higher rate of BAP1 mutation among patients of African versus European ancestry.


These findings suggest potentially significant differences in underlying tumor biology between patients of different ancestry. Additional studies are underway to better characterize differences in the gene expression profile and immune infiltrate of tumors as a function of ancestral genetics.

Presented by: Ritesh Kotecha, MD, Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Mike Lattanzi, MD, Medical Oncology & Hematology, Texas Oncology – Austin Central during the 2022 International Kidney Cancer Symposium (IKCS) North America, November 4-5, Austin, Texas, USA

email news signup