2023-11-07 22:15:40
Each cell makes its own proteins by accessing genetic information from its genes. Changes in this information, called mutations, can prevent the affected proteins from functioning normally. In oncology, this field is called cancer genetics. However, in recent decades a new field has emerged that is going strong, that of cancer epigenetics.
Epigenetic modifications do not change information, but rather they transiently modify the cell’s ability to read some of its own genes and produce associated proteins. There is a vast epigenetic program that thus controls the general functioning of the cell and, when altered, can place it on the starting line of malignant transformation. The question is, is there a way to track these changes and understand the epigenetics of the cancer transition?
An international team of researchers has begun to unravel this long-awaited milestone. In a true tour de force, they analyzed 1.7 million cells from 225 samples of primary and metastatic origin, from a group of 205 patients with 11 different types of cancer. From each cell, the team obtained the complete transcriptome, exome and epigenome. This covers virtually all genetic mutations, gene accessibility and their consequences. Thanks to its enormous computational capacity, the team has been able to deduce the complete functional state of each cell analyzed and link it to its specific type of cancer.
The results of the work, published in the academic journal Nature, demonstrate that many regions of DNA are differentially activated or inactivated in a cancer-specific manner, creating a signature for each tumor. These differences are relevant to the progression of cancer and many correspond to the already identified Hallmarks of cancer, or milestones of cancer, which are the steps that a cell must take to become malignant. Dr. Eduard Porta, group leader at the Josep Carreras Leukemia Research Institute (IJC), one of the CERCA institutions of the Generalitat of Catalonia, is part of the team of researchers that carried out the study, to which he was able to contribute his vast experience in analyzing large amounts of biological data.
Dr. Eduard Porta. (Photo: Josep Carreras Leukemia Research Institute)
Epigenetic changes at the DNA level stand out as the underlying cause of cancer, according to the new study. In particular is the accessibility of enhancer regions, a kind of master regulator that acts on many genes at the same time. Taken together, the results converge on a short list of genes that can be used as markers of good or bad prognosis, valuable information for the clinical management of patients. The analysis has also identified the cellular pathways of these important genes, allowing their interactions to be tracked at a distance.
Sometimes the affected genes are so fundamental that it is impossible to apply medication directly to them without side effects, but by knowing the complete pathway, researchers can develop strategies that target the weakest link in the chain, maximizing therapeutic benefits and minimizing undesirable effects. (Source: Josep Carreras Leukemia Research Institute)
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