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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.
Journal ArticleDOI

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 strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

TL;DR: Only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could the precise structure of the derivative chromosomes be delineated, and this study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis.
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The human leulocyte test system. VII. Further investigations concerning micronucleus-derived premature chromosome condensation.

Giinter Obe, +1 more
- 06 Nov 1975 - 
TL;DR: Premature chromosome condensation from X-ray induced micronuclei shows a dose-effect relationship in human leukocytes in vitro and the S-phase nature of "pulverized" PCC patches could be verified by incorporation of tritiated thymidine in aound 50%.
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Gene amplification: yeast takes a turn.

TL;DR: The origins of gene amplifications in mammalian cells have been difficult to analyze because of secondary genome rearrangements but recent studies in budding yeast have provided new insights into the role of palindromic sequences in gene amplification.
Journal ArticleDOI

Mechanisms for Structural Variation in the Human Genome

TL;DR: As the ability to sequence the whole human genome rapidly evolves, the diversity of SVs is illuminated, including very complex rearrangements involving multiple DSBs in a process recently designated as “chromothripsis”.
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