Oncogene responsible for every hundredth case of cancer
Researchers at the Sanger Institute, working under the leadership of Dr. David Adams, have found that inactivation of the CUX1 gene triggers a biological process that leads to the development of malignant tumors in 1% of all cancer patients. The relationship between this gene and the formation of tumors was revealed for the first time.
The authors analyzed the genetic data of more than 7,600 cancer patients collected and sequenced by the International Consortium for the Study of the Cancer Genome (ICGC) and other research groups. As a result, they found that in about 1% of the genomes studied, the CUX1 gene was inactivated as a result of various mutations.
The CUX1 gene mutates relatively rarely, but its mutations are found in cells of many types of malignant tumors. Previously, in search of mutations that trigger the process of malignant transformation of cells, experts paid attention to genes whose mutations are often found in any particular type of cancer, so the CUX1 gene has not yet attracted attention.
To understand the mechanisms underlying the revealed pattern, the authors used genetic methods to inactivate the CUX1 gene in cell culture. Observation of what is happening inside cells has shown that inactivation of this gene blocks the effect of the biological inhibitor PIK3IP1 (interacting with phosphoinositide-3-kinase protein-1), which, in turn, mobilizes the enzyme PI3K (phosphoinositide-3-kinase) responsible for cell growth, increasing the likelihood of cell malignancy.
To date, the authors have identified several dozen more rarely mutating genes, mutations of which can contribute to the formation of malignant tumors. They plan to conduct experiments on the inactivation of these genes in live mice in order to understand in detail the causes and mechanisms of tumor development.
According to Professor Paul Workman, deputy director and head of one of the departments of the London Institute of Cancer Research, drugs that inhibit the signaling mechanism mediated by phosphoinositide-3-kinase are already undergoing clinical trials, and the results of this work will help apply them to the treatment of a new group of patients.
Article by Chi C. Wong et al. Inactivating CUX1 mutations promote tumorigenesis is published in the journal Nature Genetics.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Wellcome Trust Sanger Institute:
Gene promotes one in a hundred of tumours.
10.12.2013