Abstract：
:Somatic mutations of many cancer genes tend to co-occur (termed co-mutations) in certain patterns during tumor initiation and progression. However, the genetic and epigenetic mechanisms that contribute to the co-mutations of these cancer genes have yet to be explored. Here, we systematically investigated the association between the somatic co-mutations of cancer genes and high-order chromatin conformation. Significantly, somatic point co-mutations in protein-coding genes were closely associated with high-order spatial chromatin folding. We propose that these regions be termed Spatial Co-mutation Hotspots (SCHs) and report their occurrence in different cancer types. The conserved mutational signatures and DNA sequences flanking these point co-mutations, as well as CTCF-binding sites, are also enriched within the SCH regions. The genetic alterations that are harboured in the same SCHs tend to disrupt cancer driver genes involved in multiple signalling pathways. The present work demonstrates that high-order spatial chromatin organisation may contribute to the somatic co-mutations of certain cancer genes during tumor development.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Shi Y,Su XB,He KY,Wu BH,Zhang BY,Han ZGdoi
10.1038/srep35270subject
Has Abstractpub_date
2016-10-20 00:00:00pages
35270issn
2045-2322pii
srep35270journal_volume
6pub_type
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pub_type： 杂志文章
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journal_title：Scientific reports
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