Innovative Methodology Translates Noncoding DNA in Colorectal Cancer

They searched for regulatory elements present in the vast, noncoding portion of the genome that impact the development of colorectal cancer. The goal was to identify the effect, present only in cancerous tissue, of acquired mutations whose activation would have triggered the disease and it is the first study of this scale to examine the noncoding genome of cancer patients. RNA quality was assessed using the Bioanalyzer RNA 6000 Nano Kit (Agilent Technologies; Santa Clara, CA, USA) and RNA quantity was measured with the Qubit 2.0 fluorometer using the RNA Broad range kit (Invitrogen; Carlsbad, CA, USA) and messenger RNA (mRNA) sequencing was done on a HiSeq 2000 platform (Illumina; San Diego, CA, USA).

The team was able to identify two kinds of noncoding mutations that have an impact on the development of colorectal cancer. They found, on one hand, hereditary regulatory variants that are not active in healthy tissue, but are activated in tumors and seem to contribute to cancer progression. It shows that the inherited genome not only affects the predisposition towards developing cancer, but also has an influence on its progression. On the other hand, the scientists identified effects of acquired mutations on the regulation of gene expression that affect the genesis and progression of colorectal tumors.

Halit Ongen, PhD, the lead author of this study, said, “The elements responsible for the development and progression of cancers located in the noncoding genome are as important as those found in the coding regions of the genome. Therefore, analyzing genetic factors in our whole genome, and not only in the coding regions as it was done before, gives us a much more comprehensive knowledge of the genetics behind colorectal cancer.” The study was published on July 23, 2014, in the journal Nature.

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