H2O Engineer

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Registered on: 11/30/2022

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One of the research projects led by Mitchell L. Leibowitz suggests that: “a catastrophic mutational process called chromothripsis is a previously unappreciated consequence of CRISPR-Cas9“. For those unfamiliar with chromothripsis, it is an extensive chromosome rearrangement restricted to one or a few chromosomes that can cause human congenital disease and cancer. For the layman, Fyodor Urnov, a research professor at Berkley, describes chromothripsis as being similar to rearranging a section of a jigsaw in random order with no regard for whether the resulting image makes any sense. It is accepted that chromothripsis is very common in cancer, and it is well established that it leads to tumor suppressor loss and dysregulation of genes with known cancer links. Indeed, a study published last year showed that chromothripis was present in 49% of the cancers studied.

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The mechanism by which chromothripsis occurs has not been completely explained, although a micronuclei model is the one which has gained the greatest traction amongst the scientific community. In short, mashed up DNA becomes separated from the main nucleus and forms a separate micronucleus, which then, over time, becomes reincorporated into the main nucleus. This mashed up DNA then contributes to the cell becoming carcinogenic. Chromothripsis can be generated by a single catastrophic event during the life history of a cell.

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