Structural mutations in cancer: mechanistic and functional insights

Next-generation sequencing (NGS) has enabled the comprehensive and precise identification of many somatic structural mutations in cancer. Analyses integrating point mutation information with data on rearrangements and copy number variation have revealed a higher-order organization of the seemingly r...

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Bibliographic Details
Published in:Trends in genetics 2012-11, Vol.28 (11), p.550-559
Main Authors: Inaki, Koichiro, Liu, Edison T
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cancer genome
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
chromosome structure
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Genome, Human
genomic rearrangement
Humans
Medical Education
Molecular and cellular biology
Mutation
mutational mechanisms
Neoplasms - genetics
Oncogenes
structural mutation
tandem duplication
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Summary:Next-generation sequencing (NGS) has enabled the comprehensive and precise identification of many somatic structural mutations in cancer. Analyses integrating point mutation information with data on rearrangements and copy number variation have revealed a higher-order organization of the seemingly random genetic events that lead to cancer. These meta-analyses provide a more refined view of the mutational mechanisms, genomic evolution, and combinations of mutations that contribute to tumorigenesis. Structural mutations, or genome-scale rearrangements of segments of DNA, may play a hitherto unappreciated role in cancer through their ability to move blocks of adjacent genes simultaneously, leading to concurrent oncogenic events. Moreover, whole-genome sequencing (WGS) data from tumors have revealed global rearrangements, such as those seen in the tandem duplicator phenotype and in chromothripsis, suggesting that massive rearrangements are a specific cancer phenotype. Taken together, the emerging data suggest that the chromosome structure itself functions as a systems oncogenic organizer.
ISSN:0168-9525
DOI:10.1016/j.tig.2012.07.002