Prevalence of Germline Variants in Advanced Renal Cell Carcinoma in North India
PURPOSEGenetic 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.METHODSThi...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society of Clinical Oncology
2025-07-01
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| Series: | JCO Global Oncology |
| Online Access: | https://ascopubs.org/doi/10.1200/GO-25-00137 |
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| Summary: | PURPOSEGenetic 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.METHODSThis 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.RESULTSOut 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.CONCLUSIONPatients 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. |
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| ISSN: | 2687-8941 |