Integrative genome comparison of primary and metastatic melanomas.
Integrative genome comparison of primary and metastatic melanomas.
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DOI：
10.1371/journal.pone.0010770
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发表时间：
2010-05-24
期刊：
影响因子：
3.7
通讯作者：
Chin L
中科院分区：
文献类型：
--
作者：
Kabbarah O;Nogueira C;Feng B;Nazarian RM;Bosenberg M;Wu M;Scott KL;Kwong LN;Xiao Y;Cordon-Cardo C;Granter SR;Ramaswamy S;Golub T;Duncan LM;Wagner SN;Brennan C;Chin L
恶性黑色素瘤的一个主要特征是其转移倾向。对驱动转移进展的遗传事件的不完整观点已成为合理开发有效治疗方法和黑色素瘤患者预后诊断的主要障碍。在这项研究中，我们进行了原发性和转移性黑色素瘤的全球基因组特征，以检查与转移进展相关的基因组景观。除了发现转移性黑色素瘤的三个基因组亚类外，我们还描绘了39个扩增和缺失的局灶性和复发性区域，其中许多包含与癌症或转移无关的常驻基因。为了确定进展相关的转移基因候选基因，我们采用了统计学方法，整合基因组比较（IGC），定义了32个相关的基因组区域，这些区域在转移中相对于原发性黑色素瘤发生了显著改变，其中包括30个具有统计学意义的表达失调的基因。对MET、ASPM、AKAP9、IMP3、PRKCA、RPA3和SCAP2等候选药物的功能分析证实了它们在人类黑色素瘤细胞中的促侵袭活性。Survivin的组织微阵列分析进一步证实了IGC方法的有效性，结果显示，在厚的原发性皮肤黑色素瘤与薄的原发性皮肤黑色素瘤中，IGC蛋白的表达显著增加，并且与淋巴结转移的进展相关。总之，这些功能验证结果和人体组织的相关分析支持了这样一种观点，即分期黑色素瘤的基因组和病理综合分析为发现黑色素瘤转移基因提供了一个有效的切入点。
A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes.
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影响因子：
3.8
作者：
Han W;Han MR;Kang JJ;Bae JY;Lee JH;Bae YJ;Lee JE;Shin HJ;Hwang KT;Hwang SE;Kim SW;Noh DY
通讯作者：
Noh DY
影响因子：
8
作者：
Joensson, G.;Dahl, C.;Borg, A.
通讯作者：
Borg, A.
影响因子：
11.2
作者：
Luo, Man-Li;Shen, Xiao-Ming;Wang, Ming-Rong
通讯作者：
Wang, Ming-Rong
DOI：
10.1093/jnci/djn037
发表时间：
2008-03-19
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Frank, Bernd;Wiestler, Miriam;Burwinkel, Barbara
通讯作者：
Burwinkel, Barbara
影响因子：
11.2
作者：
Brennan, C;Zhang, YY;Chin, L
通讯作者：
Chin, L