高度微卫星不稳定的晚期前列腺癌中复杂的MSH2和MSH6突变
Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer.
作者信息
Pritchard Colin C, Morrissey Colm, Kumar Akash, Zhang Xiaotun, Smith Christina, Coleman Ilsa, Salipante Stephen J, Milbank Jennifer, Yu Ming, Grady William M, Tait Jonathan F, Corey Eva, Vessella Robert L, Walsh Tom, Shendure Jay, Nelson Peter S
机构信息
Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA.
Department of Urology, University of Washington, Seattle, Washington 98195, USA.
出版信息
Nat Commun. 2014 Sep 25;5:4988. doi: 10.1038/ncomms5988.
A hypermutated subtype of advanced prostate cancer was recently described, but prevalence and mechanisms have not been well-characterized. Here we find that 12% (7 of 60) of advanced prostate cancers are hypermutated, and that all hypermutated cancers have mismatch repair gene mutations and microsatellite instability (MSI). Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing. Our findings identify parallels and differences in the mechanisms of hypermutation in prostate cancer compared with other MSI-associated cancers.
最近描述了一种晚期前列腺癌的高突变亚型，但患病率和机制尚未得到充分表征。在这里，我们发现12%（60例中的7例）的晚期前列腺癌是高突变的，并且所有高突变癌都有错配修复基因突变和微卫星不稳定性（MSI）。突变通常是复杂的MSH2或MSH6结构重排，而不是MLH1表观遗传沉默。我们的研究结果确定了前列腺癌与其他MSI相关癌症相比，高突变机制中的异同。
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