Researchers say in a new study published in the journal Nature Genetics that they have for the first time linked mutations outside the coding genes to changes in gene expression in tumors, helping to develop future diagnostic and therapeutic strategies.
Cancers develop because of uncontrolled cell growth and division, ultimately leading to the metastatic spread of cancer cells throughout the body, causing massive dysfunction of the organ. Innovative studies have shown that transformation into a cancer cell is driven by the accumulation of mutations in cellular DNA.
Researchers have clarified the effect of specific mutations on genes and have found that these mutations play an integral role in the features of cancer. This research has led to the development of many successful therapeutic methods used in the clinic today.
However, the overwhelming majority of mutations found in cancer cells are found in DNA sequences other than genes, called uncoded regions. These mutations were more difficult to study. Now in their new study, researchers have identified hundreds of mutations in uncoded regions that directly regulate the expression of genes involved in cancer formation.
“Most cancer-related mutations occur in genomic areas outside the genes, but there are so many incredibly many of those who find it difficult to know which ones are really important and which do not,” the study said.
Some attempts to understand the effect of non-mutant mutations have been made using the genomic cancer atlas (TCGA), a genome sequence data repository from both normal tissues and tumors. However, these efforts have only identified a relative non-coding mutation.
“For the first time, we found about 200 mutations in uncoded DNA that are functional in cancer – and these are about 199 more than we previously knew,” the researchers also state in their study.
The research team validated its findings by modifying the effect of these functional non-coding mutations on the cancer cellular structures. They found that these mutations directly affected the expression of genes that lead to the formation of cancer.
“An example that distinguished was an uncoded mutation that affected a gene called DAAM1. Activation of DAAM1 makes cancer cells more aggressive and more capable of invading surrounding tissues.”
The findings of the new study can help develop new diagnostic and therapeutic strategies based on the recognition of functional mutations in patient volumes.