Researchers reproduce tumor chromosomal translocations in human cells -
The research was made possible through the use of new molecular tool for manipulating the cellular genome
scientists at the National Spanish research on cancer (CNIO) and the cardiovascular research Spanish National Centre (CNIC) were able to reproduce, for the first time in human cells, chromosomal translocations associated with two types cancer: acute myeloid leukemia and Ewing sarcoma. The discovery, published today in the journal Nature Communications , opens the door to the development of new therapeutic targets to fight against these types of cancer.
The study was conducted by Sandra Rodriguez-Perales - from CNIO Molecular Cytogenetics Group, led by Juan Cruz Cigudosa - and Juan Carlos Ram-ground and the Ra-Torres, the viral vector Technical Unit of CNIC . Researchers have shown that it is possible to produce chromosomal changes in human cells which are genetically identical to those observed in leukemia and other types of human cancer.
This new technology offers two key benefits based on the use of molecular tools for manipulating the genome: first, working models that has not existed until now to study the biology of the tumor and, secondly, their application will eventually to the study of new therapeutic targets and therapies
alterations. leading to the development of the tumor due to multiple changes in cell physiology and in particular into the genome of the cell. In leukemia and other tumors called sarcomas, exchanges of large DNA fragments occur between different chromosomes, a phenomenon known as chromosomal translocations. As the authors of the study highlight these translocations are necessary both for the generation and progression of a number of neoplastic processes.
"The study of this type of tumors has been problematic until now because of the lack of cellular models and relevant animal models," said Juan Carlos CNIC researcher Ram-ground, which adds that the difficulty of producing these chromosomal translocations had limited availability of cells that mark the disease.
Breaking chromosomes to study cancer
Using endonuclease (RGEN) technology or CRISPR RNA-guided / case.9 technology of genome engineering, the CNIO researchers CNIC and showed that it is possible to get these chromosomal translocations. In this way, they managed to replicate chromosomal translocations in human stem cells from blood and mesenchymal tissue that are identical to those observed in patients with acute myeloid leukemia (a blood and bone marrow cancer) or Ewing's sarcoma (a type of bone tumor affecting children and adolescents).
"With this breakthrough, it is possible to generate cell models with the same changes as those observed in tumor cells of patients, allowing us to study their role in tumor development "said CNIO researcher Sandra Rodr guez-Perales,. "This way it is possible to experimentally summarize the next steps necessary for normal cells to turn into cancer cells."
The researchers used the powerful RGEN tool, which was developed in early 2013, for the manipulation of genes in eukaryotic cells, including humans. It is based on the design of a small RNA (RNAsg) which is complementary and specific to a DNA region of 20 nucleotides. The binding of RNAsg DNA acts as a signal for the enzyme case.9 to produce a cut on the edge of the marked DNA. The system is very effective and specific and allows cuts to be made in double helix of DNA where researchers need to.
Rodr-guez-Perales, Torres and Ram-ground have shown that the transfer of the Rgen components in primary human cells, chromosomal regions exchanged in some tumors may be labeled, thereby generating cuts in chromosomes.
"When the DNA repair machinery attempts to repair these breaks, it causes the generation of a translocation between two different chromosomes, in many cases mutually between the two chromosomes involved," says researcher CNIC Ra -l Torres.
the study authors conclude by stating that the use of this technology will also allow clarification of how and why the translocation occurs, which probably allow new therapeutic strategies anti- to tackle cancer.
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