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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 ArticleDOI

Identification of complex genomic rearrangements in cancers using CouGaR

TL;DR: CouGaR is introduced, a novel method for characterizing the genomic structure of amplified CGRs, leveraging both depth of coverage (DOC) and discordant pair-end mapping techniques, and identified amplified C GRs in at least 5.2% of whole-genome sequencing samples from The Cancer Genome Atlas.
Journal ArticleDOI

Genomic Instability Promoted by Overexpression of Mismatch Repair Factors in Yeast: A Model for Understanding Cancer Progression.

TL;DR: In this article, the authors used the Cancer Genome Atlas and Gene Expression across Normal and Tumor tissue databases to analyze MMR protein expression in cancers and found that the MMR genes MSH2 and MSH6 are overexpressed more frequently than MSH3.
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Low MiR-187 Expression Promotes Resistance to Chemoradiation Therapy In Vitro and Correlates with Treatment Failure in Patients with Esophageal Adenocarcinoma

TL;DR: One of these miRNAs, miR-187, was significantly decreased in pretreatment EAC tumors from patients having a poor response to neoadjuvant CRT, highlighting downregulation of miR -187 as a potential mediator of treatment resistance in EAC.
Journal ArticleDOI

Suppressing proteasome mediated processing of topoisomerase II DNA-protein complexes preserves genome integrity

TL;DR: Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability.
References
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Journal ArticleDOI

Hallmarks of cancer: the next generation.

TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
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Signatures of mutational processes in human cancer

Ludmil B. Alexandrov, +84 more
- 22 Aug 2013 - 
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Journal ArticleDOI

Cancer Genome Landscapes

TL;DR: This work has revealed the genomic landscapes of common forms of human cancer, which consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of "hills" (Genes altered infrequently).
Journal ArticleDOI

The clonal evolution of tumor cell populations

TL;DR: Each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment, which should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
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