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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

A DNA Replication Mechanism for Generating Nonrecurrent Rearrangements Associated with Genomic Disorders

TL;DR: Analysis of junction sequences in PMD patients confirms the occurrence of simple tandem PLP1 duplications but also uncovers evidence for sequence complexity at some junctions, consistent with a replication-based mechanism that is termed FoSTeS, for replication Fork Stalling and Template Switching.
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Human aneuploidy: mechanisms and new insights into an age-old problem

TL;DR: New studies of humans and model organisms have shed new light on the complexity of meiotic defects, providing evidence that the age-related increase in errors in the human female is not attributable to a single factor but to an interplay between unique features of oogenesis and a host of endogenous and exogenous factors.
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Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis

TL;DR: The mitotic checkpoint is a major cell cycle control mechanism that guards against chromosome missegregation and the subsequent production of aneuploid daughter cells.
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