Algorithm identifies unknown driver mutations in cancer cells
2022
German Cancer Research Center (DKFZ), Heidelberg, Germany
The development and spread of malignant tumors is associated with the increased occurrence of mutations. In the coding area of the genome, cancer-causing gene segments can already be identified as far as possible. The non-coding area, which includes important regulatory sequences, has so far remained unexplored due to methodological limitations. The distinction between driver mutations and neutral "passenger" mutations is particularly difficult. The present study describes a newly developed algorithm (sigDriver) that detects changes in the genetic material and evaluates them with regard to their cancer driver potential. The research group investigated three characteristic mutation signatures associated with the emergence of hotspots. For this purpose, the genetic material of a total of 3813 tumors was analyzed, whose entire genome had been sequenced as part of the International Cancer Genome Consortium (ICGC), The Cancer Genome Atlas program, as well as in a study on pediatric tumors. The new method follows an automated search-then-annotate approach; i.e. all mutations that the algorithm classified as carcinogenic were analyzed by means of differential expression analysis and annotation. The algorithm unerringly identified all already known hotspots, as well as presumed new drivers in the coding as well as non-coding area and enables a valid differentiation of driver and passenger mutations. The method can help to uncover further, unknown cancer drivers (especially in the regulatory field) in larger patient cohorts with the same type of cancer and is freely available to researchers worldwide.
Association of mutation signature effectuating processes with mutation hotspots in driver genes and non-coding regions
Marc Zapatka, John K. L. Wong
Added on: 08-12-2022
[1] https://www.nature.com/articles/s41467-021-27792-6[2] https://www.bionity.com/en/news/1174259/algorithm-identifies-cancer-drivers.html
