Chromothripsis

Chromothripsis is the name for a genetic phenomenon in which triggered in a cell occurs by a one-time event to a variety of rearrangements of chromosome segments. It was discovered in cells from patients with various cancers in 2011.

Description

The phenomenon of chromothripsis was first described in 2011 in a paper in the journal Cell by scientists at the Wellcome Trust Sanger Institute in Cambridge, who discovered it in a patient with chronic lymphocytic leukemia and also the appropriate term coined. The cells of this patient showed 42 rearrangements in clusters localized on the long arm of chromosome 4. In cells from further examined patients with other cancers, other chromosome regions, entire chromosomes or more chromosomes were moreover affected simultaneously. Nature and distribution of changes in the chromosomes suggest that this did not occur as part of an ongoing process, but all the result of the same and designated by the authors as "catastrophic" or as " cellular crisis " event are, in which to multiple it chromosome breakage occurs. The authors estimated on the basis of their results, that such an event takes place in two to three percent of all cancers a role, with an accumulation of up to a quarter of all cases of bone tumors. A later published by Harvard University researchers analysis of over 8000 cancer genomes confirmed this estimate.

Contrary to what would be expected with such a massive destruction of the chromosome structure, die by the affected cells probably not by apoptosis. Rather, it appears to succeed the mechanisms of DNA repair in some cells, the chromosomes partially reassemble, whereby the cell to survive under certain circumstances. This leads to a variety of deletions, duplications, inversions and translocations for the merger of previously adjacent chromosome segments. Result of these changes, which are inherited through cell division, is then a loss of function of tumor suppressor genes. According to the first to describe this phenomenon is likely to occur when the chromosomes during mitosis in fused form. As a possible trigger they suspect among other radioactive radiation or a connection with the stretching and compression of the chromosomes during the shortening of telomeres at the ends of chromosomes in the cell division.

In 2012, Heidelberg scientists described in the journal Cell that the medulloblastoma, a malignant early childhood tumor of the cerebellum, chromothripsis associated with hereditary mutations of the TP53 gene occurs ( Li -Fraumeni syndrome). A concomitant loss of the p53 protein, which is also known as the " guardian of the genome ", is a possible explanation for why there as a result of chromothripsis despite massive destruction of the chromosome structure does not initiate cell death by apoptosis or to a termination of the cell cycle comes. In addition to cancers comparable with the chromothripsis form of destruction of chromosomes has also been described for congenital diseases. In an article published in the journal Cell in March 2013 article several criteria are described that can be used to detect the chromothripsis in genomic data.