Showers of Mutations

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Science  08 Jun 2012:
Vol. 336, Issue 6086, pp. 1211
DOI: 10.1126/science.336.6086.1211-c

Systematic cataloging of somatic mutations in cancer genomes not only helps identify specific genes driving tumor development but can also potentially reveal clues to the endogenous or environmental factors that caused the mutations in the first place. Lung and melanoma genomes, for example, have mutational patterns characteristic of tobacco carcinogens and ultraviolet light, respectively. Nik-Zainal et al. have begun to explore the mutational processes operative in human breast cancer. By documenting the full repertoire of somatic mutations in 21 different tumors and using mathematical approaches to classify them, they discovered that single-nucleotide substitutions in breast cancer appear to be generated by at least five independent mutational processes. Mutations were more prevalent in genes expressed at low levels. Most of the tumors exhibited regional clusters of hypermutation (called “kataegis,” Greek for shower), which were closely associated with regions of chromosomal rearrangements. The authors hypothesize that these mutations are caused by the AID/APOBEC family of cytidine deaminases, which generate somatic hypermutation in the immune system.

Cell 149, 979 (2012).

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