Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution.
Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution.
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DOI：
10.1016/j.ccell.2018.06.005
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发表时间：
2018-07-09
期刊：
影响因子：
50.3
通讯作者：
Bastian BC
中科院分区：
文献类型：
--
作者：
Shain AH;Joseph NM;Yu R;Benhamida J;Liu S;Prow T;Ruben B;North J;Pincus L;Yeh I;Judson R;Bastian BC
我们通过对原发性黑色素瘤及其邻近前体以及匹配的原发性肿瘤和区域转移瘤的DNA和RNA进行测序，阐明了伴随黑色素瘤从癌前病变演变而来的基因组和转录组变化。总之，我们分析了82例患者的230个组织病理学不同的黑素细胞瘤变区域。体细胞改变依次诱导丝裂原活化蛋白激酶（MAPK）通路激活、端粒酶上调、染色质景观调节、G1/S检查点覆盖、MAPK信号传导斜升、p53通路破坏和PI 3 K通路激活;没有突变与转移进展特异性相关，因为这些通路在原发性黑色素瘤演变过程中受到干扰。紫外线辐射诱导的点突变稳步增加，直到黑色素瘤的入侵，在这一点上，拷贝数的变化也变得普遍。Shain等人显示了在从癌前病变到黑色素瘤的演变过程中连续的MAPK途径激活、端粒酶上调、染色质景观调节、G1/S检查点覆盖、MAPK信号传导斜升、p53途径破坏和PI 3 K途径激活，但没有转移特异性突变。
We elucidated genomic and transcriptomic changes that accompany the evolution of melanoma from premalignant lesions by sequencing DNA and RNA from primary melanomas and their adjacent precursors, as well as matched primary tumors and regional metastases. In total, we analyzed 230 histopathologically distinct areas of melanocytic neoplasia from 82 patients. Somatic alterations sequentially induced mitogen-activated protein kinase (MAPK) pathway activation, upregulation of telomerase, modulation of the chromatin landscape, G1/S checkpoint override, ramp-up of MAPK signaling, disruption of the p53 pathway, and activation of the PI3K pathway; no mutations were specifically associated with metastatic progression, as these pathways were perturbed during the evolution of primary melanomas. UV radiation-induced point mutations steadily increased until melanoma invasion, at which point copy-number alterations also became prevalent. Shain et al. show sequential MAPK pathway activation, telomerase upregulation, chromatin landscape modulation, G1/S checkpoint override, MAPK signaling ramp-up, p53 pathway disruption, and PI3K pathway activation during the evolution from pre-malignant lesions to melanoma, but no metastasis-specific mutations.
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影响因子：
3.7
作者：
Ding L;Kim M;Kanchi KL;Dees ND;Lu C;Griffith M;Fenstermacher D;Sung H;Miller CA;Goetz B;Wendl MC;Griffith O;Cornelius LA;Linette GP;McMichael JF;Sondak VK;Fields RC;Ley TJ;Mulé JJ;Wilson RK;Weber JS
通讯作者：
Weber JS
种系PTEN突变患者的终生癌症风险。
DOI：
10.1158/1078-0432.ccr-11-2283
发表时间：
2012-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Tan MH;Mester JL;Ngeow J;Rybicki LA;Orloff MS;Eng C
通讯作者：
Eng C
影响因子：
30.8
作者：
Krauthammer, Michael;Kong, Yong;Ha, Byung Hak;Evans, Perry;Bacchiocchi, Antonella;McCusker, James P.;Cheng, Elaine;Davis, Matthew J.;Goh, Gerald;Choi, Murim;Ariyan, Stephan;Narayan, Deepak;Dutton-Regester, Ken;Capatana, Ana;Holman, Edna C.;Bosenberg, Marcus;Sznol, Mario;Kluger, Harriet M.;Brash, Douglas E.;Stern, David F.;Materin, Miguel A.;Lo, Roger S.;Mane, Shrikant;Ma, Shuangge;Kidd, Kenneth K.;Hayward, Nicholas K.;Lifton, Richard P.;Schlessinger, Joseph;Boggon, Titus J.;Halaban, Ruth
通讯作者：
Halaban, Ruth
影响因子：
30.8
作者：
Krauthammer M;Kong Y;Bacchiocchi A;Evans P;Pornputtapong N;Wu C;McCusker JP;Ma S;Cheng E;Straub R;Serin M;Bosenberg M;Ariyan S;Narayan D;Sznol M;Kluger HM;Mane S;Schlessinger J;Lifton RP;Halaban R
通讯作者：
Halaban R
影响因子：
28.2
作者：
Shi H;Hugo W;Kong X;Hong A;Koya RC;Moriceau G;Chodon T;Guo R;Johnson DB;Dahlman KB;Kelley MC;Kefford RF;Chmielowski B;Glaspy JA;Sosman JA;van Baren N;Long GV;Ribas A;Lo RS
通讯作者：
Lo RS