Comprehensive genomic profiling of 216 Chinese patients with renal cell carcinoma.

Abstract

3532 Background: Renal cell carcinoma (RCC), a global public health problem, has exhibited a gradual rise in incidence. Unfortunately, the scarcity of effective biomarkers in the clinical became a major limitation of the progress of biological therapies. Therefore, it is imperative to accurately comprehend RCC genomic profiling for exploring its clinical treatment strategies. Methods: Formalin Fixed Paraffin Embedded (FFPE) tumor and matched blood samples of 216 Chinese RCC patients were obtained for next-generation sequencing (NGS)-based 620 cancer genes panel assay and RCC genomic profiling was evaluated. Results: In our Chinese RCC cohort, multiple histological subtypes, encompassing clear cell (96/216, 44.44%), papillary (14/216, 6.48%), chromophobe (2/216, 0.93%), and undefined subtypes (104/216, 48.15%) were included. The top ranked genomic alterations in Chinese RCC patients were VHL (45.83%), PBRM1 (17.1%), BAP1(13.89%), TP53 (10.65%), SETD2 (9.29%), MTOR (8.67%), ARID1A (5.6%), PTEN (5.09%). Interestingly, BAP1, PBRM1 were co-mutated with VHL, and MET, NF2 were mutually exclusive with VHL (all p < 0.05). Of these patients, 87.9% (190/216) of RCC patients had at least one genomic alteration, indicating the potential clinical benefits of targeted therapies. Out of 15 most common canonical pathways, potentially targetable genomic alterations were mainly identified in HIF (45.83%), chromatin remodeling (42.59%), PI3K/AKT (24.07%), DNA damage response (19.44%), RTK-RAS (18.06%), TP53 (15.74%), NOTCH (9.72%), Hippo (9.72%), and WNT (5.56%) pathway. Additionally, HIF pathway was commonly co-altered with chromatin remodeling pathway, and WNT and NOTCH pathways were significantly co-altered with TP53 pathway. Rare mutation types such as CDKN2A-DMRTA1 and HOOK1-ALK were also detected. Across samples, the median TMB was 2.2 (0-18.6) mutations/Mb. Only 2 Chinese RCC patients had TMB-high (> 10 mutations/Mb). Conclusions: Our results displayed the landscape of genomic alterations in 216 Chinese RCC patients. The genomic alterations identified in our study may provide an opportunity to discover potential strategies for targeted and immunotherapy in RCC. Future studies should account for these genomic alterations.