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Published on: January 31, 2018
Chromothripsis from DNA damage in micronuclei.
Cheng-Zhong Zhang1, Alexander Spektor2, Hauke Cornils3
11] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [3] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [4] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Chromothripsis, a genomic rearrangement phenomenon in cancer, can be caused by chromosomes isolated in micronuclei. This study demonstrates micronucleus formation leads to chromothripsis-like events within a single cell division.
Area of Science:
- Genomics
- Cell Biology
- Cancer Research
Background:
- Chromothripsis is a mutational phenomenon characterized by extensive genomic rearrangements on limited chromosomes.
- The underlying mechanism of chromothripsis remains largely unknown.
- A prior hypothesis suggested chromothripsis may arise from chromosomes isolated within micronuclei.
Purpose of the Study:
- To investigate the role of micronuclei in generating genomic rearrangements.
- To determine if micronucleus formation can recapitulate chromothripsis.
- To elucidate the mechanism of chromothripsis.
Main Methods:
- Live cell imaging
- Single-cell genome sequencing
- Micronucleus formation induction
Main Results:
- Micronucleus formation can generate a spectrum of genomic rearrangements.
- These rearrangements, including chromothripsis features, are restricted to mis-segregated chromosomes.
- Chromothripsis-like events can occur within a single cell division via fragmentation and reassembly within micronuclei.
Conclusions:
- Micronucleus formation is a viable mechanism for generating chromothripsis.
- This study establishes a novel mutational process with chromothripsis as an extreme outcome.
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