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Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements

TLDR
The impact of massive chromosomal change for the development of diseases such as cancer and for evolution more generally is considered and current models for underlying mechanisms are summarized.
Abstract
Recent genome sequencing studies have identified several classes of complex genomic rearrangements that appear to be derived from a single catastrophic event. These discoveries identify ways that genomes can be altered in single large jumps rather than by many incremental steps. Here we compare and contrast these phenomena and examine the evidence that they arise "all at once." We consider the impact of massive chromosomal change for the development of diseases such as cancer and for evolution more generally. Finally, we summarize current models for underlying mechanisms and discuss strategies for testing these models.

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Patterns of Somatic Mutation in Human Cancer Genomes

TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.
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Spatial and temporal diversity in genomic instability processes defines lung cancer evolution

TL;DR: 25 spatially distinct regions from seven operable NSCLCs were sequenced and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification, and pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity.
Journal ArticleDOI

Endogenous DNA Damage as a Source of Genomic Instability in Cancer

Anthony T. Tubbs, +1 more
- 09 Feb 2017 - 
TL;DR: Recent studies that shed light on endogenous sources of mutation and epigenomic features that promote genomic instability during cancer evolution are reviewed.
Journal ArticleDOI

Chromothripsis from DNA damage in micronuclei

TL;DR: It is demonstrated that micronucleus formation can indeed generate a spectrum of genomic rearrangements, some of which recapitulate all known features of chromothripsis.
Journal ArticleDOI

DNA double-strand break repair-pathway choice in somatic mammalian cells.

TL;DR: This Review considers DSB repair-pathway choice in somatic mammalian cells as a series of ‘decision trees’, and explores how defective pathway choice can lead to genomic instability.
References
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Journal ArticleDOI

The Pattern of Gene Amplification Is Determined by the Chromosomal Location of Hairpin-Capped Breaks

TL;DR: Using yeast as a model system, it is found that hairpin-capped double-strand breaks occurring at the location of human Alu-quasipalindromes lead to the formation of intrachromosomal amplicons with large inverted repeats or extrachromOSomal palindromic molecules.
Journal ArticleDOI

Chromothripsis and Human Disease: Piecing Together the Shattering Process

TL;DR: The unprecedented resolution of high-throughput genomics has enabled the recent discovery of a phenomenon by which specific regions of the genome are shattered and then stitched together via a single devastating event, referred to as chromothripsis.
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Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes

TL;DR: An algorithm for detecting regions in which the copy number oscillates rapidly between fixed levels, indicative of chromothripsis is developed, and this comprehensive view of copy number alterations provides a framework for understanding the functional significance of various genomic alterations in cancer genomes.
Journal ArticleDOI

Recombination-restarted replication makes inverted chromosome fusions at inverted repeats

TL;DR: It is proposed that the error-prone nature of restarted forks contributes to the generation of GCRs and gene amplification in cancer, and to non-recurrent CNVs in genomic disorders.
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