New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis.
New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis.
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DOI：
10.1016/j.celrep.2015.09.037
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发表时间：
2015-10-27
期刊：
影响因子：
8.8
通讯作者：
Larue L
中科院分区：
文献类型：
--
作者：
Rambow F;Job B;Petit V;Gesbert F;Delmas V;Seberg H;Meurice G;Van Otterloo E;Dessen P;Robert C;Gautheret D;Cornell RA;Sarasin A;Larue L
设计针对耐药肿瘤的治疗方法需要针对特定肿瘤类型的分子特征。然而，目前尚不清楚肿瘤和用于药物开发的相应细胞系是否具有这样的特征。我们开发了相似性核心分析（SCA），这是一种通用且无监督的计算框架，用于提取肿瘤和细胞系共有的核心分子特征。我们将 SCA 应用到来自不同来源的 mRNA/miRNA 表达数据，比较黑色素瘤细胞系和转移瘤。获得的特征与体外表型特征相关，核心基因CAPN3和TRIM63与黑色素瘤细胞迁移/侵袭有关。约 90% 的黑色素瘤特征基因属于控制神经发育的转录因子（TFAP2A、DLX2、ALX1、MITF、PAX3、SOX10、LEF1 和 GAS7）和 miRNA（211-5p、221-3p 和 10a-5p）的内在网络。 SCA 特征有效地区分了总体存活率不同的两个黑色素瘤患者亚群，并对 MEKi/BRAFi 耐药和敏感的黑色素瘤细胞系进行了分类。癌细胞系处于药物发现的最前沿，但由于人工培养条件，在代表肿瘤起源方面往往受到限制。兰博等人。开发一种用于识别肿瘤细胞谱系表达核心的计算方法。这些核心基因揭示了与攻击性、患者生存和药物敏感性相关的相关分子依赖性。
Molecular signatures specific to particular tumor types are required to design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used for drug development share such signatures. We developed similarity core analysis (SCA), a universal and unsupervised computational framework for extracting core molecular features common to tumors and cell lines. We applied SCA to mRNA/miRNA expression data from various sources, comparing melanoma cell lines and metastases. The signature obtained was associated with phenotypic characteristics in vitro, and the core genes CAPN3 and TRIM63 were implicated in melanoma cell migration/invasion. About 90% of the melanoma signature genes belong to an intrinsic network of transcription factors governing neural development (TFAP2A, DLX2, ALX1, MITF, PAX3, SOX10, LEF1, and GAS7) and miRNAs (211-5p, 221-3p, and 10a-5p). The SCA signature effectively discriminated between two subpopulations of melanoma patients differing in overall survival, and classified MEKi/BRAFi-resistant and -sensitive melanoma cell lines. Cancer cell lines are at the forefront of drug discovery but are often limited in representing the tumor of origin due to the artificial culture conditions. Rambow et al. develop a computational approach for identifying tumor cell lineage expression cores. These core genes reveal relevant molecular dependencies linking aggressiveness, patient survival, and drug sensitivity.
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影响因子：
64.5
作者：
Basu A;Bodycombe NE;Cheah JH;Price EV;Liu K;Schaefer GI;Ebright RY;Stewart ML;Ito D;Wang S;Bracha AL;Liefeld T;Wawer M;Gilbert JC;Wilson AJ;Stransky N;Kryukov GV;Dancik V;Barretina J;Garraway LA;Hon CS;Munoz B;Bittker JA;Stockwell BR;Khabele D;Stern AM;Clemons PA;Shamji AF;Schreiber SL
通讯作者：
Schreiber SL
影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
9.2
作者：
Daniele, Tiziana;Hurbain, Ilse;Schiaffino, Maria Vittoria
通讯作者：
Schiaffino, Maria Vittoria
DOI：
10.1111/j.1600-0749.2006.00322.x
发表时间：
2006-08-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Hoek, Keith S.;Schlegel, Natalie C.;Dummer, Reinhard
通讯作者：
Dummer, Reinhard
影响因子：
6.5
作者：
Bell, Rachel E.;Khaled, Mehdi;Levy, Carmit
通讯作者：
Levy, Carmit