Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling
Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling
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DOI：
10.1200/jco.2003.10.108
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发表时间：
2003-05-01
影响因子：
45.3
通讯作者：
Houghton, AN
中科院分区：
文献类型：
--
作者：
Segal, NH;Pavlidis, P;Houghton, AN
目的：建立透明细胞肉瘤（CCS）（也称为软组织黑色素瘤（MSP））基于基因组的分类方案，这将对诊断和治疗产生影响。该肿瘤显示了软组织肉瘤（STS）的特征，包括深部软组织原发位置和特征性易位，t（I 2; 22）（cl 1 3;q12），涉及EWS和ATF 1基因。CCS/MSP也具有典型的黑色素瘤特征，包括S 100和HMB 45的免疫反应性、色素沉着、MITF-M表达和区域淋巴结转移的倾向。材料和方法：使用U95 A基因芯片（Affyphon，Santa Clara，CA）检查来自21个细胞系和60个病理证实的STS、黑色素瘤和CCS/MSP病例的RNA样品。层次聚类分析，主成分分析，支持向量机（SVM）分析利用基因组相关性内的数据进行分类CCS/MSP。结果：无监督分析表明STS和黑色素瘤之间有明显的区别，此外，表明CCS/MSP集群与黑色素瘤作为一个独特的组。有监督的SVM学习方法进一步验证了这一发现，并提供了一个独立于用户的诊断方法。感兴趣的基因，区分CCS/MSP包括那些编码黑素细胞分化抗原，MITF，SOX 10，ERBB 3，和FGFR I。结论：基因表达谱支持CCS/MSP作为一个独特的基因组亚型黑色素瘤的分类。使用SVM分析这些基因谱可能是一个重要的诊断工具。基因组分析确定了开发治疗该病的治疗策略的潜在靶点。(C)2003年，美国临床肿瘤学会。
Purpose : To develop a genome-based classification scheme for clear-cell sarcoma (CCS), also known as melanoma of soft parts (MSP), which would have implications for diagnosis and treatment. This tumor displays characteristic features of soft tissue sarcoma (STS), including deep soft tissue primary location and a characteristic translocation, t(I 2; 22)(cl 1 3;q12), involving EWS and ATF1 genes. CCS/MSP also has typical melanoma features, including immunoreactivity for S 100 and HMB45, pigmentation, MITF-M expression, and a propensity for regional lymph node metastases.Materials and Methods: RNA samples from 21 cell lines and 60 pathologically confirmed cases of STS, melanoma, and CCS/MSP were examined using the U95A GeneChip (Affymetrix, Santa Clara, CA). Hierarchical cluster analysis, principal component analysis, and support vector machine (SVM) analysis exploited genomic correlations within the data to classify CCS/MSP.Results: Unsupervised analyses demonstrated a clear distinction between STS and melanoma and, furthermore, showed that CCS/MSP cluster with the melanomas as a distinct group. A supervised SVM learning approach further validated this finding and provided a user-independent approach to diagnosis. Genes of interest that discriminate CCS/MSP included those encoding melanocyte differentiation antigens, MITF, SOX10, ERBB3, and FGFR I.Conclusion: Gene expression profiles support the classification of CCS/MSP as a distinct genomic subtype of melanoma. Analysis of these gene profiles using the SVM may be an important diagnostic tool. Genomic analysis identified potential targets for the development of therapeutic strategies in the treatment of this disease. (C) 2003 by American Society of Clinical Oncology.