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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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Journal Article

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

Mechanisms for recurrent and complex human genomic rearrangements.

TL;DR: Progress is described in explaining nonallelic homologous recombination (NAHR), a major cause of copy number change occurring when control of allelic recombination fails, the growing importance of replicative mechanisms to explain complex events, and progress in understanding extreme chromosome reorganization (chromothripsis).
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The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line

TL;DR: Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis.
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Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells.

TL;DR: p53-deficient mouse embryonic fibroblasts were used to establish a direct mechanism of tumor suppression by p53 involving the destruction of oncogene-expressing cells by apoptosis and p53 mutation could enhance the survival of malignant cells expressing oncogenes activated early in tumor progression.
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Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline

TL;DR: The pattern of random joining of chromosomal fragments that is observed here strongly resembles the somatic rearrangement patterns--termed chromothripsis--that have recently been described in deranged cancer cells and it is concluded that a similar mechanism may also drive the formation of de novo structural variation in the germline.
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Characterization of uterine leiomyomas by whole-genome sequencing.

TL;DR: Chromosome shattering and reassembly resembling chromothripsis is a major cause of chromosomal abnormalities in uterine leiomyomas and it is proposed that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events.
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