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Novel mutational process targeting gene regulatory elements discovered

Date:
June 8, 2015
Source:
University of Helsinki
Summary:
Researchers discovered previously uncharacterized mutational patterns in the human regulatory genome, especially in gastrointestinal tract cancers. Unraveling the underlying mechanisms of regulatory mutations in cancer remains a great challenge. The novel findings from this study are significant and an important step towards understanding the cause and consequences of cancer-associated mutations, the researchers say.
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The research led by Academy Professor Lauri Aaltonen and Professor Jussi Taipale, was based on study of more than two hundred whole genomes of colorectal cancer samples. The scientists detected a distinct accumulation of mutations specifically at sites where the proteins CTCF and cohesin bind the DNA.

Both CTCF and cohesin are transcription factors carrying out essential functions in the genome, including regulation of gene expression and chromatin structure. In hypermutated tumors, the CTCF/cohesin sites appear to be protected from mutations while in a distinct set of tumors, CTCF/cohesin sites are mutated with frequency higher than previously known protein coding cancer genes. Tumors with high CTCF site mutation load tend to have greater frequency of certain type of mutations distributed throughout their genome. The process producing these mutations is not fully understood and needs further investigation.

Until now the mutational patterns of the regulatory genome are poorly characterized. Unraveling the underlying mechanisms of regulatory mutations in cancer remains a great challenge. The novel findings from this study are significant and an important step towards understanding the cause and consequences of cancer-associated mutations.

"The findings of this study were totally unexpected; they uncover the second face of the cancer genome. However, we have a lot of work to do for understanding about the reasons and consequences of these changes," Professor Aaltonen states.


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Materials provided by University of Helsinki. Note: Content may be edited for style and length.


Journal Reference:

  1. Riku Katainen, Kashyap Dave, Esa Pitkänen, Kimmo Palin, Teemu Kivioja, Niko Välimäki, Alexandra E Gylfe, Heikki Ristolainen, Ulrika A Hänninen, Tatiana Cajuso, Johanna Kondelin, Tomas Tanskanen, Jukka-Pekka Mecklin, Heikki Järvinen, Laura Renkonen-Sinisalo, Anna Lepistö, Eevi Kaasinen, Outi Kilpivaara, Sari Tuupanen, Martin Enge, Jussi Taipale, Lauri A Aaltonen. CTCF/cohesin-binding sites are frequently mutated in cancer. Nature Genetics, 2015; DOI: 10.1038/ng.3335

Cite This Page:

University of Helsinki. "Novel mutational process targeting gene regulatory elements discovered." ScienceDaily. ScienceDaily, 8 June 2015. <www.sciencedaily.com/releases/2015/06/150608120141.htm>.
University of Helsinki. (2015, June 8). Novel mutational process targeting gene regulatory elements discovered. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/06/150608120141.htm
University of Helsinki. "Novel mutational process targeting gene regulatory elements discovered." ScienceDaily. www.sciencedaily.com/releases/2015/06/150608120141.htm (accessed May 23, 2017).

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