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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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Driver and Passenger Mutations in Cancer

TL;DR: Frequency-based and function-based approaches have been developed to identify candidate drivers of cancer development; the advantages and drawbacks of these methods are discussed as well as their latest refinements.
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Tumor evolution: Linear, branching, neutral or punctuated?☆

TL;DR: Data is discussed that supports the theory that most human tumors evolve from a single cell in the normal tissue, and suggests that models may change during tumor progression or operate concurrently for different classes of mutations.
Journal ArticleDOI

Redox Signaling by Reactive Electrophiles and Oxidants

TL;DR: This Review reflects on five aspects critical for understanding how nature harnesses these noncanonical post-translational modifications to coordinate distinct cellular activities: specific players and their generation, physicochemical properties, mechanisms of action, methods of interrogation, and functional roles in health and disease.
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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