Genomic landscape and clinical actionability of renal cell carcinoma in an Indian cohort: A real-world targeted next-generation sequencing study

doi:10.5306/wjco.123328

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World Journal of Clinical Oncology

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2218-4333

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Clin Oncol. Aug 24, 2026; 17(8): 123328
Published online Aug 24, 2026. doi: 10.5306/wjco.123328

Genomic landscape and clinical actionability of renal cell carcinoma in an Indian cohort: A real-world targeted next-generation sequencing study

Vineet Talwar, Arpit Jain, Varun Goel, Bhumi Agarwal, Prateek Gupta, Rupal Tripathi, Sudhir Rawal, Anurag Mehta

Vineet Talwar, Arpit Jain, Varun Goel, Bhumi Agarwal, Prateek Gupta, Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, India

Rupal Tripathi, Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, Delhi, India

Sudhir Rawal, Department of Uro Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, Delhi, India

Anurag Mehta, Department of Laboratory, Molecular Diagnosis and Transfusion Services, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, Delhi, India

Co-corresponding authors: Arpit Jain and Varun Goel.

Author contributions: Talwar V and Jain A conceptualized and supervised the study, contributed to study design, interpreted the clinical findings, critically revised the manuscript for important intellectual content, and approved the final version; Goel V contributed to patient management, clinical data acquisition, interpretation of findings, critical manuscript revision, and approved the final version; Agarwal B participated in clinical data collection, data verification, literature review, manuscript revision, and approved the final version; Gupta P contributed to clinical data collection, interpretation of clinical findings, manuscript review, and approved the final version; Tripathi R contributed to study methodology, data management, statistical analysis, interpretation of results, manuscript revision, and approved the final version; Rawal S contributed to patient selection, clinical management, interpretation of urological and oncological findings, critical revision of the manuscript, and approved the final version; Mehta A supervised molecular diagnostic testing and next-generation sequencing analysis, interpreted molecular findings, contributed to the molecular pathology components of the manuscript, critically revised the manuscript for scientific accuracy, and approved the final version; Jain A and Goel V played important and indispensable roles in the manuscript preparation as the co-corresponding authors; all authors reviewed the final manuscript, approved the submitted version, and agree to be accountable for all aspects of the work.

AI contribution statement: AI-assisted tools, including ChatGPT (OpenAI) and Grammarly, were used solely to assist with English language editing, grammar correction, sentence refinement, readability improvement, and manuscript formatting under the direct supervision of the authors. AI tools were not used for study conception, data collection, data analysis, statistical analysis, interpretation of results, generation of scientific content, or formulation of conclusions. All scientific content, data interpretation, and the final manuscript were independently reviewed, verified, and approved by the authors, who accept full responsibility for the integrity, accuracy, originality, and scientific validity of the manuscript.

Institutional review board statement: This study was reviewed and approved by the Institutional Ethics Committee of Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India (approval No. Res/SCM/41/2020/101). The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Informed consent statement: The requirement for individual informed consent was waived by the Institutional Ethics Committee because of the retrospective nature of the study and the use of anonymized clinical and genomic data. No identifiable patient information was included in this study.

Conflict-of-interest statement: All authors declare that they have no conflicts of interest relevant to this study.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement- checklist of items.

Data sharing statement: The datasets generated and/or analyzed during the current study are not publicly available because they contain institutional clinical and genomic data that could compromise patient confidentiality. De-identified data may be made available by the corresponding author upon reasonable request, subject to approval by the Institutional Ethics Committee and applicable institutional regulations.

Corresponding author: Arpit Jain, Consultant, Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, Rohini, New Delhi 110085, India. jain.arpit@rgcirc.org

Received: May 20, 2026
Revised: July 15, 2026
Accepted: August 14, 2026
Published online: August 24, 2026
Processing time: 101 Days and 23 Hours

Abstract

BACKGROUND

Renal cell carcinoma (RCC) demonstrates extensive genomic heterogeneity. While major sequencing projects like The Cancer Genome Atlas have defined key molecular causes; real-world genomic data from Indian population is limited. This study intends to define the mutational landscape of RCC in an Indian tertiary cancer center and to evaluate the clinical actionability of identified alterations using the European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT).

AIM

To characterize the genomic landscape of RCC in an Indian real-world cohort using targeted next-generation sequencing (NGS) and to evaluate the clinical actionability of detected alterations according to the ESCAT.

METHODS

This retrospective real-world investigation included 48 patients with pathologically diagnosed RCC who underwent tumor genomic profiling with a focused 14-gene NGS panel encompassing chromatin-remodeling genes, DNA damage repair (DDR) pathways, and the PI3K-AKT-mTOR signaling axis. Clinicopathological features were collected and genetic changes were categorized by ESCAT tiers to assess potential clinical significance.

RESULTS

The cohort comprised 75% males with a median age of 58 years. Clear cell RCC (ccRCC) was the most common histology (81.3%) and advanced disease (American Joint Committee on Cancer stage III/IV) was found in 56.2% of patients. The most frequently altered genes were VHL (35.4%), PBRM1 (25.0%), SETD2 (14.6%), ATM (12.5%), and TP53 (12.5%). In the ccRCC subgroup (n = 39), mutation frequencies for VHL and PBRM1 were 38.5% and 25.6%, respectively. The most prevalent co-alteration pattern was VHL-PBRM1 mutations (n = 6). ESCAT analysis showed potentially actionable alterations in 18.8% of cases, mostly Tier II/III variants in the PI3K-AKT-mTOR pathway (MTOR, TSC1/TSC2, PIK3CA) and Tier III/IV alterations in DDR genes.

CONCLUSION

This study delineates the real-world genomic landscape of RCC in an Indian cohort, confirming key chromatin-remodeling alterations characteristic of ccRCC while suggesting relatively higher frequencies of ATM and TP53 mutations. Although targeted NGS provides important molecular insights, the proportion of high-tier actionable alterations remains limited, underscoring the need for broader genomic profiling and biomarker-driven studies in this population.

Keywords: Clear cell renal cell carcinoma; Next-generation sequencing; Precision oncology; Real-world data; European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets

Core Tip: Renal cell carcinoma (RCC) demonstrates significant molecular heterogeneity; however, genomic data from Indian patients remain limited. In this real-world single-center study, targeted next-generation sequencing identified recurrent alterations in VHL, PBRM1, SETD2, ATM, and TP53, with concurrent VHL-PBRM1 mutations representing the most frequent co-alteration pattern. Potentially actionable alterations, primarily involving the PI3K-AKT-mTOR pathway, were detected in a subset of patients based on the European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets. These findings provide important insights into the genomic profile and therapeutic implications of RCC in an underrepresented population.