AUTHOR=Zhou Wenyang , Yang Fan , Xu Zhaochun , Luo Meng , Wang Pingping , Guo Yu , Nie Huan , Yao Lifen , Jiang Qinghua 

TITLE=Comprehensive Analysis of Copy Number Variations in Kidney Cancer by Single-Cell Exome Sequencing

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01379

DOI=10.3389/fgene.2019.01379

ISSN=1664-8021

ABSTRACT=<p>Clear-cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of kidney cancer. <italic>VHL</italic> and <italic>PBRM1</italic> are the top two significantly mutated genes in ccRCC specimens, while the genetic mechanism of the <italic>VHL/PBRM1</italic>-negative ccRCC remains to be elucidated. Here we carried out a comprehensive analysis of single-cell genomic copy number variations (CNVs) in <italic>VHL/PBRM1</italic>-negative ccRCC. Genomic CNVs were identified at the single-cell level, and the tumor cells showed widespread amplification and deletion across the whole genome. Functional enrichment analysis indicated that the amplified genes are significantly enriched in cancer-related signaling transduction pathways. Besides, receptor protein tyrosine kinase (RTK) genes also showed widespread copy number variations in cancer cells. Our studies indicated that the genomic CNVs in RTK genes and downstream signaling transduction pathways may be involved in <italic>VHL/PBRM1</italic>-negative ccRCC pathogenesis and progression, and highlighted the role of the comprehensive investigation of genomic CNVs at the single-cell level in both clarifying pathogenic mechanism and identifying potential therapeutic targets in cancers.</p>