Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma
Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma
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DOI：
10.1002/path.4204
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发表时间：
2013-07-01
影响因子：
7.3
通讯作者：
Marais, Richard
中科院分区：
文献类型：
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作者：
Furney, Simon J.;Turajlic, Samra;Marais, Richard
与皮肤黑色素瘤相比，粘膜黑色素瘤表现出独特的临床和流行病学特征。在这里，我们使用全基因组和全外显子组测序来表征十种粘膜黑色素瘤基因组中的体细胞改变和突变谱。我们观察到体细胞突变率远低于暴露在阳光下的皮肤黑色素瘤中的发生率，但与与暴露于已知诱变剂无关的癌症中观察到的突变率相当。特别是，突变特征并不表明紫外线或烟草烟雾引起的 DNA 损伤。先前报道在其他癌症中发生突变的基因在粘膜黑色素瘤中也发生了突变。值得注意的是，粘膜黑色素瘤中的拷贝数和结构变异比皮肤黑色素瘤中报道的要多得多。因此，粘膜和皮肤黑色素瘤是具有不同遗传特征的不同疾病。我们的数据表明，这些疾病的发生有不同的机制，并且结构变异在粘膜黑色素瘤发生中比在皮肤黑色素瘤发生中发挥更重要的作用。版权所有 (c) 2013 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Mucosal melanoma displays distinct clinical and epidemiological features compared to cutaneous melanoma. Here we used whole genome and whole exome sequencing to characterize the somatic alterations and mutation spectra in the genomes of ten mucosal melanomas. We observed somatic mutation rates that are considerably lower than occur in sun-exposed cutaneous melanoma, but comparable to the rates seen in cancers not associated with exposure to known mutagens. In particular, the mutation signatures are not indicative of ultraviolet light- or tobacco smoke-induced DNA damage. Genes previously reported as mutated in other cancers were also mutated in mucosal melanoma. Notably, there were substantially more copy number and structural variations in mucosal melanoma than have been reported in cutaneous melanoma. Thus, mucosal and cutaneous melanomas are distinct diseases with discrete genetic features. Our data suggest that different mechanisms underlie the genesis of these diseases and that structural variations play a more important role in mucosal than in cutaneous melanomagenesis. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.