An international study conducted by Stanford University, the University of Illinois and the Val d'Hebron Institute of Oncology (VHIO) has developed and validated a technology capable of identifying genetic changes that cause cancer, known as Drivers.
Research published in the magazine Cell reportsIt was based on the investigation of sArithmetic staging With the aim of identifying amplifications in the number of gene copies that could be linked to tumorigenesis. He analyzed the frequency of these changes and linked them to changes in gene expression.
The authors of the research explain that cancer cells need one or more modifications in their DNA that cause them to divide and multiply uncontrolled, which is called Drivers. Some of these changes consist of an increase in specific regions of the genome in the number of DNA copies. Specifically, due to the fact that these regions can be very broad, in many cases it is not known which gene is at work. driver Within this area, which can lead to the development of cancer.
Thus, as the study authors explained, the researchers caused amplification of the barcode-tagged copy number by infecting the cDNA with the lentivirus. The organisms were subsequently cultured and sequenced to determine the numbers of distinct genes. The higher the number of copies, the more likely it is that the gene is actually one driver.
With the computational approach, the study made it possible to reduce the number of candidate genes Drivers to about 1000. Of these genes, a subset of 393 candidate genes has been validated in mouse and human organoids (3D models of organs created in the laboratory) of cancers of the esophagus, oral cavity, colon, stomach, pancreas and lung. Thus, according to the researchers, the results of the study confirm the validity of the use of this technique and confirm the identification of two new species Drivers In esophageal cancer and oral cavity cancer.
“Using the barcode and lentivirus system, we were able to identify several oncogenes already known as CDK4, CDK6 or KRAS in these types of cancer, and validate the new methodology,” explains Dr. José Antonio Siwan, head of the Computational Biology Group at UCLA. illinois. “In addition, we were able to identify two new ones Drivers It indicates that oncogenic FGF3 in esophageal cancer and DYRK2 in oral cavity cancer.
According to the researcher, the study not only demonstrates the usefulness of this system in detection Drivers This treatment could stimulate cancer development, but it also opens the door to investigating whether an FGF3 inhibitor approved in the United States for bladder and gallbladder cancer would be effective in patients with esophageal cancer, which typically has a poor prognosis.
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