Comprehensive genomic profiling in Chinese patients with clear cell renal cell carcinoma.

e13517 Background: Clear cell renal cell carcinoma (ccRCC) represents the most common histological subtype of RCC, with poor response to chemotherapy and radiotherapy. Immunotherapy and novel therapies targeting angiogenesis signaling pathways have proved to be effective for RCC patients (pts). However, the comprehensive genomic features of ccRCC in Chinese pts have not been well understood. Methods: Deep sequencing targeting 450 cancer genes was performed on FFPE and matched blood samples collected from 39 Chinese ccRCC pts with a median age of 54 years (range 31-75) and a male-to-female ratio of 3.3. Genomic alterations (GAs) including single nucleotide variations, short and long insertions and deletions, copy number variations, and gene rearrangements were analyzed. Tumor mutation burden (TMB) and microsatellite instability (MSI) status were assessed by standard NGS algorithms. Results: In the Chinese cohort, the most common genomic alterations were detected in VHL (82.1%), PBRM1 (53.8%), SETD2 (20.5%), PTEN (15.4%), BAP1 (17.9%), TSC1/2 (15.4%), TP53 (10.3%), TERT (7.7%), MTOR (7.7%), KMT2C (7.7%), and CHD2 (7.7%). In total, 80% of the pts had one or more actionable GAs. The chromosome 3p tumor suppressors (VHL, PBRM1, and SETD2) were identified in 87% of the pts. PI3K/mTOR pathway alterations including PTEN, MTOR, TSC1/2 and PIK3CA mutations were detected in 30% of the pts. Compared with TCGA data (501 pts), we found higher mutation frequency of VHL, PBRM1, and PTEN in the current Chinese cohort. The median TMB value of our ccRCC pts was 5.6 muts/Mb (range: 0-58); 8.3% of the pts had TMB greater than or equal to 20 muts/Mb. Three ccRCC pts were identified as MSI-H. One pt with a novel MET fusion responded well to cabozantinib. Conclusions: Compared with the TCGA data set mostly based on Western population, our Chinese cohort revealed that the genomic alteration frequencies of chromosome 3p tumor suppressors (VHL, PBRM1, and SETD2) were higher compared with TCGA (VHL: 82.1% vs 49.3%; PBRM1: 53.8% vs 30.1%; SETD2: 20.5% vs 12.4%). The NGS-based comprehensive genomic profiling assay could detect all GAs, TMB, and MSI status simultaneously, and suggest personalized treatment options of targeted therapy and immunotherapy for ccRCC pts.