Abstract：
:Genome sequencing has uncovered a new mutational phenomenon in cancer and congenital disorders called chromothripsis. Chromothripsis is characterized by extensive genomic rearrangements and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes. The mechanism for chromothripsis is unknown, but we previously proposed that it could occur through the physical isolation of chromosomes in aberrant nuclear structures called micronuclei. Here, using a combination of live cell imaging and single-cell genome sequencing, we demonstrate that micronucleus formation can indeed generate a spectrum of genomic rearrangements, some of which recapitulate all known features of chromothripsis. These events are restricted to the mis-segregated chromosome and occur within one cell division. We demonstrate that the mechanism for chromothripsis can involve the fragmentation and subsequent reassembly of a single chromatid from a micronucleus. Collectively, these experiments establish a new mutational process of which chromothripsis is one extreme outcome.
journal_name
Naturejournal_title
Natureauthors
Zhang CZ,Spektor A,Cornils H,Francis JM,Jackson EK,Liu S,Meyerson M,Pellman Ddoi
10.1038/nature14493subject
Has Abstractpub_date
2015-06-11 00:00:00pages
179-84issue
7555eissn
0028-0836issn
1476-4687pii
nature14493journal_volume
522pub_type
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