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Updated: Sep 16, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Prevalence of Germline Variants in Advanced Renal Cell Carcinoma in North India
Chitrakshi Nagpal1, Mohit Kumar Divakar1, Hemavathi Baskarane1
1Department of Medical Oncology, Dr B.R.A. IRCH, AIIMS, New Delhi, India.
Purpose:
Genetic predisposition plays an important role in the pathogenesis of renal cell carcinoma. The prevalence of pathogenic/likely pathogenic (P/LP) in patients with renal cell cancer (RCC) is highly variable, and close to 40% of these can be missed with the current testing guidelines.
Methods:
This is a prospective study of all patients with metastatic RCC unselected for high-risk features, registered at our center between September 2023 and August 2024. Baseline clinicopathologic details were collected, and germline whole-exome sequencing was done on blood samples. Our aim was to determine the frequency of germline mutations in an unselected cohort of patients with metastatic RCC. Germline P/LP variants were visualized using cBioPortal, and chi-square and Mann-Whitney U tests were used to identify differences in patients with/without these variants.
Results:
Out of 140 participants, P/LP variants in cancer-predisposition genes were detected in 20%, and 4.2% were in RCC-associated genes. Fumarate hydratase was the most common RCC-associated variant (2.8%), while WT1, BRCA1, BRIP1, and ATM (1.4% each) were the commonest non-RCC-associated variants. RCC-associated genes were more frequent in non-clear cell histology (P = .02); there was no difference in cancer predisposition genes on the basis of age, histology, or sex.
Conclusion:
Patients with advanced RCC have a high prevalence of germline variants in both RCC-associated and non-RCC cancer-specific genes irrespective of the high-risk genetic features, signifying the importance of a baseline genetic evaluation in all patients with advanced RCC as it has implications for family screening and, in future, selection of therapy.
