Abstract
Using a dataset of somatic Structural Variants (SVs) in cancers from 2658 patients—1220 with corresponding gene expression data—we identified hundreds of genes for which the nearby presence (within 100kb) of an SV breakpoint was associated with altered expression. For the vast majority of these genes, expression was increased rather than decreased with corresponding SV event. Well-known up-regulated cancer-associated genes impacted by this phenomenon included TERT, MDM2, CDK4, ERBB2, and IGF2. For specific gene categories, associated SVs were found to potentially impact on the order of 2-4% of cases across various types. SVs upstream of TERT involved ~3% of cancer cases and were most frequent in liverbiliary, melanoma, sarcoma, stomach, and kidney cancers. For many genes, SVs were significantly associated with either an increase or decrease in the numbers of enhancer regulatory elements near the promoter. DNA methylation near the gene promoter was often increased with nearby SV breakpoint.
Abbreviations
- PCAWG
- the Pan-Cancer Analysis of Whole Genomes project
- SV
- Structural Variant