Genomic Classification of Cutaneous Melanoma.
Genomic Classification of Cutaneous Melanoma.
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DOI：
10.1016/j.cell.2015.05.044
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发表时间：
2015-06-18
期刊：
影响因子：
64.5
通讯作者：
Cancer Genome Atlas Network
中科院分区：
文献类型：
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作者：
Cancer Genome Atlas Network
我们通过对331名患者的333例原发和/或转移性黑色素瘤的DNA、RNA和基于蛋白质的分析，描述了皮肤黑色素瘤的基因组变化情况。我们根据最常见的显著突变基因的模式，建立了一个基因组分类框架，将其分为四个亚型之一：突变的BRAF、突变的RAS、突变的NF1和三重WT(野生型)。综合分析显示，作为Triple-WT亚型的一个特征，KIT突变和焦点扩增丰富，以及复杂的结构重排。我们发现与基因组分类没有显著的结果相关性，但样本在病理回顾中指定了与淋巴细胞浸润性相关的免疫基因表达丰富的转录亚类，以及T细胞标记物LCK蛋白的高表达与患者存活率的改善有关。这一临床病理和多维分析表明，黑色素瘤区域转移患者的预后受到肿瘤间质免疫生物学的影响，为进一步个性化治疗决策提供了见解。
We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multidimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.