Structural mutations in cancer: mechanistic and functional insights.
Document Type
Article
Publication Date
11-1-2012
JAX Source
Trends Genet 2012 Nov; 28(11):550-9.
PMID
22901976
ISSN
0168-9525
Abstract
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.
Recommended Citation
Inaki K,
Liu E.
Structural mutations in cancer: mechanistic and functional insights. Trends Genet 2012 Nov; 28(11):550-9.