Until now, scientists have repeatedly examined only the coding regions of the genome to find the genetic basis of different cancers. Yet, these well-reviewed regions constitute just two percent of the total, with the remaining 98 percent of the genome consisting of non-coding DNA and other elements — altogether referred to as junk DNA. Though they didn't understand the function of these unexplored elements, many scientists suspected they might regulate gene expression and so play a critical role in the development of cancer and other diseases. Now, new research has identified genetic mutations that contribute to colorectal cancer in the non-coding portion of the human genome. 

The Human Genome and Junk DNA

Your genome is all of your genes taken together. With the mapping of the human genome (completed in 2003), scientists discovered that the genome consists of about 20,500 genes and of these, only about two percent are coding DNA — those transcribing the blueprint for making proteins — while non-coding DNA constituted the vast majority (98 percent) of the genome. Among the genes you inherit from your parents, you also inherit strong or weak predispositions to developing cancer, which is a disease resulting from genetic mutation. You also accumulate mutations in your cells throughout your lifetime. To understand how cancer develops, then, scientists explore both the hereditary and acquired genetic mutations that trigger tumor development.

The one thing they have never studied, though, are the mutations taking place in the non-coding portion of the genome, the junk DNA considered to be relatively functionless... until now.

To understand the role of junk DNA in cancer development, Dr. Emmanouil Dermitzakis, a professor of genetics at University of Geneva, and his colleagues focused their efforts on a study of colorectal cancer. Using genome sequencing technology, the team of geneticists compared healthy tissue and tumor tissue from 103 patients, searching for elements in the vast, non-coding portion of the genome that might impact the development of colorectal cancer. The UNIGE team was able to identify two kinds of non-coding mutations that have an impact on the development of colorectal cancer. First, hereditary mutations, passive in healthy tissue, were found to be active in tumors and seemed to contribute to cancer progression. Second, the researchers also observed how the mutations acquired over time regulated gene expression and affected both the genesis and progression of colorectal tumors.

“The elements responsible for the development and progression of cancers located in the non-coding genome are as important as those found in the coding regions of the genome,” explained Dr. Halit Ongen, lead author of this study. “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.” This methodology, Dermitzakis noted, is not exclusive to colorectal cancer but can be applied to other types of cancer as well.

Source: Ongen H, Andersen CL, Bramsen JB, et al. Putative cis-regulatory drivers in colorectal cancer. Nature. 2014.