Molecular Oncology Group, Cancer Research UK Manchester Institute, Wilmslow Road, Manchester, M20 4BX, UK.
J Pathol. 2013 Jul;230(3):261-9. doi: 10.1002/path.4204.
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.
与皮肤黑色素瘤相比，黏膜黑色素瘤表现出明显不同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描述十个黏膜黑色素瘤基因组中的体细胞改变和突变谱。我们观察到的体细胞突变率明显低于暴露于阳光的皮肤黑色素瘤中的突变率，但与与已知诱变剂无关的癌症中的突变率相当。特别是，突变特征并不表明与紫外线或烟草烟雾引起的 DNA 损伤有关。以前在其他癌症中报告为突变的基因在黏膜黑色素瘤中也发生了突变。值得注意的是，黏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，黏膜和皮肤黑色素瘤是具有不同遗传特征的两种截然不同的疾病。我们的数据表明，这些疾病的发生机制不同，结构变异在黏膜黑色素瘤的发生中比在皮肤黑色素瘤的发生中起更重要的作用。
