Novel mutational process targeting gene regulatory elements discovered

Researchers found previously uncharacterized mutational patterns in gastrointestinal tract cancers

2015-06-08

(Press-News.org) Researchers at University of Helsinki, Finland, and Karolinska Institutet, Sweden, discovered previously uncharacterized mutational patterns in the human regulatory genome, especially in gastrointestinal tract cancers. The study was published in Nature Genetics. 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.

INFORMATION:

The research was funded by Academy of Finland Centre of Excellence for Cancer Genetics, Jane and Aatos Erkko Foundation and EU FP7 project SYSCOL. For more information, please contact: Academy Professor Lauri Aaltonen
Tel. +358-40-4435041
E-mail: lauri.aaltonen@helsinki.fi END

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Novel mutational process targeting gene regulatory elements discovered

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