Comprehensive characterization and clinical relevance of the SWI/SNF copy number aberrations across human cancers

Hereditas

Weiting Sun¹  Buhuan Ma¹  Yimin Sun²  Zhiwei Xing³  Caixia Liu³ 

[1] Inner Mongolia Medical University, 010050, Hohhot, Inner Mongolia, China;National Engineering Research Center for Beijing Biochip Technology, 102206, Beijing, China;Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, 100084, Beijing, China;The Affiliated Hospital of Inner Mongolia Medical University, 010050, Hohhot, Inner Mongolia, China;

关键词: SWI/SNF complex;    Copy number alteration;    Immune cell infiltration;    Genome instability;   

DOI  :  10.1186/s41065-021-00203-y

来源: Springer

【 摘 要 】

BackgroundAlterations in genes encoding chromatin regulatory proteins are prevalent in cancers and may confer oncogenic properties and molecular changes linked to therapy resistance. However, the impact of copy number alterations (CNAs) of the SWItch/Sucrose NonFermentable (SWI/SNF) complex on the oncogenic and immunologic properties has not been systematically explored across human cancer types.MethodsWe comprehensively analyzed the genomic, transcriptomic and clinical data of The Cancer Genome Atlas (TCGA) dataset across 33 solid cancers.ResultsCNAs of the SWI/SNF components were identified in more than 25% of all queried cancers, and tumors harboring SWI/SNF CNAs demonstrated a worse overall survival (OS) than others in several cancer types. Mechanistically, the SCNA events in the SWI/SNF complex are correlated with dysregulated genomic features and oncogenic pathways, including the cell cycle, DNA damage and repair. Notably, the SWI/SNF CNAs were associated with homologous recombination deficiency (HRD) and improved clinical outcomes of platinum-treated ovarian cancer. Furthermore, we observed distinct immune infiltrating patterns and immunophenotypes associated with SWI/SNF CNAs in different cancer types.ConclusionThe CNA events of the SWI/SNF components are a key process linked to oncogenesis, immune infiltration and therapeutic responsiveness across human cancers.

【 授权许可】

CC BY