Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.
Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.
复制标题
DOI：
10.1016/j.cell.2016.05.069
复制
发表时间：
2016-07-28
期刊：
影响因子：
64.5
通讯作者：
CPTAC Investigators
中科院分区：
文献类型：
--
作者：
Zhang H;Liu T;Zhang Z;Payne SH;Zhang B;McDermott JE;Zhou JY;Petyuk VA;Chen L;Ray D;Sun S;Yang F;Chen L;Wang J;Shah P;Cha SW;Aiyetan P;Woo S;Tian Y;Gritsenko MA;Clauss TR;Choi C;Monroe ME;Thomas S;Nie S;Wu C;Moore RJ;Yu KH;Tabb DL;Fenyö D;Bafna V;Wang Y;Rodriguez H;Boja ES;Hiltke T;Rivers RC;Sokoll L;Zhu H;Shih IM;Cope L;Pandey A;Zhang B;Snyder MP;Levine DA;Smith RD;Chan DW;Rodland KD;CPTAC Investigators
为了提供与卵巢癌相关的分子组分和潜在机制的详细分析，我们对先前由癌症基因组图谱（TCGA）分析的174个卵巢肿瘤进行了全面的基于质谱的蛋白质组学表征，其中169个是高级别浆液性癌（HGSC）。将我们的蛋白质组学测量与基因组数据相结合，对疾病产生了许多见解，例如不同的拷贝数变化如何影响蛋白质组，与染色体不稳定性相关的蛋白质，不同基因组重排汇聚的信号通路集，以及与短总生存期最相关的信号通路。与同源重组缺陷相关的特定蛋白质乙酰化提示了对患者进行分层治疗的潜在手段。除了提供有价值的资源外，这些发现还提供了体细胞基因组如何驱动癌症蛋白质组以及HGSC中蛋白质和翻译后修饰水平与临床结果之间的关联的观点。
To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSC). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease such as how different copy number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, as well as the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC.