A Survey of Cancer Cell Lines Reveals Highly Structured and Hierarchical Relationships within and between DNA and mRNA That May Be the Result of Selection

摘要

Copy number variation (CNV) is one of the most profound forms of somatic DNA changes that underlie most human cancers. However, the degree of complexity within and between DNA and mRNA variations in cancer cohorts has yet to be fully characterized. Here we characterized the connectivity of CNV/CNV and its contribution to transcriptome in human cancer cell lines. Strikingly, we found there is a significant nonrandom correlation of many unlinked DNA loci and also a significant association between CNV and mRNA expression in cis and in trans (called eCNV). Both distributions of DNA/DNA and DNA/mRNA associations exhibit a scale-free structure showing that, for DNA/DNA, a few loci correlate tomany other loci, whereas most loci correlate to only a few loci; and for DNA/mRNA, certain chromosomal loci associate with many mRNAs and that many mRNAs are controlled by more than one locus. This suggests that a small number of DNA loci act as hubs in a hierarchical structure that is highly nonrandom in nature, and genes linking to these hot spots tend to be involved in similar biological functions. Derivation of highly connected structures suggests a process of undirected copy number changes followed by selection of those advantageous to tumor cells during tumorigenesis. Given that the cohort includes many tissue types, our observations may identify a common and important underlying structure present in human tumors.