Catalog of mutations underlying carcinogenesis
The genetic origins of cancer have been found
21 major mutational processes behind the 30 most common cancers have been identified. According to the authors, whose work was published on August 14 in the journal Nature (Alexandrov et al., Signatures of mutational processes in human cancer), the map of mutations compiled by them reveals the genetic origins of cancer and gives a new understanding of the causes and ways of developing oncological diseases, which can lead to a breakthrough in their therapy and prevention.
The authors analyzed almost five million cellular mutations isolated in the genomes of 7,042 cancer patients and identified 21 variants of the mutation process, signs of which are present in varying amounts in the genomes of all 30 types of malignant tumors.
It was found that different types of cancer correspond to a different number of such variations. For example, ovarian cancer is based on two mutational processes, and liver cancer is based on six such processes. At the same time, some mutational variants correspond to several types of cancer at once, and some are characteristic of only one. For example, a variant associated with a mutation in the BRCA1 and BRCA2 genes that increase the risk of breast cancer also underlies ovarian and pancreatic cancer. Of the 30 types of malignant neoplasms, 25 were associated with age-related mutational processes. All this reflects the complexity of biological processes occurring during carcinogenesis, the authors note.
Diagram from an article in Nature – VMAnother discovery made during the study was the discovery of the fact that more than half of the types of cancer are associated with antiviral enzymes APOBEC.
The mutagenic activity of these proteins produced by the immune system that protect cells from viruses has been revealed recently. As the authors suggest, during activation in response to a viral infection, APOBEC enzymes damage the genome, causing DNA mutations leading to cancer.
Earlier, the same group described the phenomenon it identified – in breast cancer, a huge number of mutations occur in a relatively small part of the genome. In the course of this study, they found that this effect, called by the authors kataegis (kataegis), from the Greek word "storm", is present in most types of cancer. The authors suggest that the trigger triggering this hypermutation process is precisely the activation of APOBEC enzymes in response to the virus.
"We actually conducted archaeological excavations and uncovered those underground passages through which there is a hidden preparation for the development of a malignant process for the time being," says the leader of the group, director of the Wellcome Trust Sanger Institute, Professor Sir Mike Stratton (Mike Stratton). "This catalog of mutational variations and a deep look at the biological processes underlying them allows us to make significant progress in understanding carcinogenesis, which will certainly have a powerful impact on cancer prevention and treatment strategies."
Portal "Eternal youth" http://vechnayamolodost.ru15.08.2013