Abstract 2530: Understanding cancer heterogeneity in relation to minor sub-clones at single cell profiling level in renal cell carcinoma

Renal cell carcinoma (RCC) is one of the most lethal urological malignancies that would benefit from understanding cancer heterogeneity to identify molecular signatures providing potential innovative therapeutic targets. Renal cell carcinoma is characterized by extensive cancer heterogeneity. Single cell sequencing has the potential to improve our understanding of cancer heterogeneity by providing clonotype detection. We examined cancer heterogeneity using single-cell copy-number analysis and clonotype detection in four renal cancer tumors. The technology used for processing single cell was 10x ChromiumTM Technology that provides detection of 100 Kb CNV events, calling clonotypes down to 10 of 1000 cell inputs. By processing each of the four samples it resulted 469 total cells from sample one where 268 were tumor and 171 were normal; sample two resulted with 888 cells where 51 were tumor and 820 were normal; sample three resulted with 673 total cells where 167 were tumor and 485 normal; finally, sample four resulted with 1298 cells where 511 were tumor and 758 normal. Genome-wide ploidy analysis of the four tumor cells showed variable median ploidies. The regional copy number was estimated by processing our data in 20 Kb cases of reads. Multiple sub-clones were identified in sample number one where four clusters of sub-clones characterized cancer heterogeneity. Fast maximum-likelihood (ML) genetic clustering and Bayesian Information Criterion (BIC) were implemented on sample one to select the optimal clustering solution and provide a better insight of sub-clonal evolution. These sub-clones reported events such as copy number changes on entire chromosomes arms. The single cell resolution provided the ability of variant detection where we identified VHL gene mutations that are consistent with recent reports that describe its role as a molecular signature of disease outcome and drug efficacy in RCC. In conclusion, our findings describe sub-clones with large-scale events that provide new insights in understanding cancer heterogeneity in RCC. Citation Format: Enrique I. Velazquez Villarreal, John D. Carpten, David W. Craig. Understanding cancer heterogeneity in relation to minor sub-clones at single cell profiling level in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2530.