26 June 2013

The list of "cancer genes" can be reduced hundreds of times

Not all mutations in cancer-related genes can lead to its development

ABC MagazineCurrently, many genes associated with the development of cancer are known, but mutations in far from all of them can cause the disease.

American researchers have proposed a method by which it is possible to assess which genes really play a role in the development of cancer, and which ones can be ignored. Thanks to the new approach, the list of genes associated with one type of cancer has been reduced from 450 to 11 positions. This will help improve the accuracy of diagnostic tests. The results of the scientists' study are published in the journal Nature (Lawrence et al., Mutational heterogeneity in cancer and the search for new cancer-associated genes).

The journal BioTechniques published a short retelling of the work (Whittling Down the Cancer Gene List) with a link to the Broad Institute website section with a description of the MutSig (Mutation Significance) program – VM.

All cells accumulate mutations, but the tumor genome is literally stuffed with errors in DNA. This is due to the fact that cancer cells divide faster than other cells in the body, as well as the fact that cancer inactivates its own "repair" system of cells. However, most of these mutations do not affect the cell life cycle and, therefore, are not involved in the development of cancer. To find out which mutations are really important and which are not, Gad Getz and his colleagues from the Broad Institute in Cambridge have developed a new computer model that compared the genomes of various tumors and tracked which mutations are most common in all cases of cancer.


The algorithm for screening out unnecessary "suspects" by the MutSig program. Drawing from the website broadinstitute.org – VM.

The researchers assumed that as a result of the analysis, the number of mutations associated with cancer would decrease significantly compared to those already known. Instead, the list has increased. To understand why this happened, the researchers decided to evaluate other factors affecting the frequency of mutations. They found that genes that are less frequently transcribed into RNA are more susceptible to mutations, which, however, will not play a special role in the risk of cancer. The scientists also analyzed how often mutations occur during DNA replication. As it turned out, the genes that are copied last are copied with errors more often than others. All these mutations can lead to a false positive result in a diagnostic test, but the risk of the disease itself will remain extremely low.

Once all these factors were taken into account in the model, the researchers were convinced that the development of cancer is influenced by a much smaller number of genes. Thus, the risk of developing one of the types of cancer is affected by only 11 mutations, and not 450, as previously thought. The scientists' new model has already been implemented in ongoing cancer genome sequencing projects. The authors of the model hope that it will help researchers focus their attention on studying really important genes and not waste time on other, less significant ones.

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