The availability of murine tumor models recapitulating these phenomena would substantially facilitate the investigation of the mechanistic aspects underlying complex genome rearrangements.
Resynthesis of fragments from one chromatid and frequent insertions of short sequences between the rearrangement junctions are associated with copy number gains and retention of heterozygosity 2. Conversely, the local rearrangements arising from chromoanasynthesis exhibit altered copy number due to serial microhomology-mediated template switching during DNA replication 2. The outcome is a highly rearranged derivative chromosome, with oscillations between two or three copy number states 6. The DNA fragments resulting from this shattering event are re-ligated by error-prone repair processes, with some of the fragments being lost. The first form, chromothripsis, is characterized by the simultaneous occurrence of tens to hundreds of clustered DNA double-strand breaks 1, 5. These two types of catastrophic events play a role in numerous tumor entities, as well as in some congenital diseases 3, 4. Chromothripsis and chromoanasynthesis are two forms of genomic instability that lead to complex genomic rearrangements affecting one or very few chromosomes 1, 2, 3.
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