An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer.
An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer.
复制标题
DOI：
10.1186/1755-8794-6-33
复制
发表时间：
2013-09-22
影响因子：
2.7
通讯作者：
Amundadottir LT
中科院分区：
文献类型：
--
作者：
Jia J;Parikh H;Xiao W;Hoskins JW;Pflicke H;Liu X;Collins I;Zhou W;Wang Z;Powell J;Thorgeirsson SS;Rudloff U;Petersen GM;Amundadottir LT
胰腺癌是一种高度致命的癌症，诊断和治疗方式有限。为了开始探索胰腺癌的基因组景观，我们使用大规模平行测序来分类和比较来自正常和癌性胰腺的两种人类细胞系中的转录区域和潜在调控元件。通过RNA测序，我们在这些细胞系中鉴定了2，146个差异表达的基因，这些基因在癌症相关途径和生物学过程中富集，包括细胞粘附，生长因子和受体活性，信号传导，转录和分化。我们的高通量染色质免疫沉淀（ChIP）序列分析进一步鉴定了超过100，000个富含表观遗传标记的区域，显示出与基因表达的正相关（H3K4me1，H3K4me3，RNA Pol II）或负相关（H3K27me3）。值得注意的是，与正常来源的细胞系相比，在癌症来源的细胞系中观察到RNA Pol II结合的总体富集和H3K27me3结合的消耗。通过基于这种差异选择用于进一步评估的基因，我们证实了与正常来源的组织相比，在两组较大的胰腺癌细胞系和肿瘤组织中醛脱氢酶1A3（ALDH1A3）的表达增强。由于乙醛脱氢酶（ALDH）活性是癌症干细胞的一个关键特征，我们的研究结果表明，ALDH超家族的成员ALDH1A3可能在胰腺癌中上调，它可以标记胰腺癌干细胞。
Pancreatic cancer is a highly lethal cancer with limited diagnostic and therapeutic modalities. To begin to explore the genomic landscape of pancreatic cancer, we used massively parallel sequencing to catalog and compare transcribed regions and potential regulatory elements in two human cell lines derived from normal and cancerous pancreas. By RNA-sequencing, we identified 2,146 differentially expressed genes in these cell lines that were enriched in cancer related pathways and biological processes that include cell adhesion, growth factor and receptor activity, signaling, transcription and differentiation. Our high throughput Chromatin immunoprecipitation (ChIP) sequence analysis furthermore identified over 100,000 regions enriched in epigenetic marks, showing either positive (H3K4me1, H3K4me3, RNA Pol II) or negative (H3K27me3) correlation with gene expression. Notably, an overall enrichment of RNA Pol II binding and depletion of H3K27me3 binding were seen in the cancer derived cell line as compared to the normal derived cell line. By selecting genes for further assessment based on this difference, we confirmed enhanced expression of aldehyde dehydrogenase 1A3 (ALDH1A3) in two larger sets of pancreatic cancer cell lines and in tumor tissues as compared to normal derived tissues. As aldehyde dehydrogenase (ALDH) activity is a key feature of cancer stem cells, our results indicate that a member of the ALDH superfamily, ALDH1A3, may be upregulated in pancreatic cancer, where it could mark pancreatic cancer stem cells.
登录
查看更多内容
影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5
作者：
Lee, KM;Yasuda, H;Ouellette, MM
通讯作者：
Ouellette, MM
miR-182 作为神经胶质瘤进展和患者生存的预后标志物
影响因子：
6
作者：
Jiang, Lili;Mao, Pu;Li, Jun
通讯作者：
Li, Jun
影响因子：
30.8
作者：
Jacobs, Kevin B.;Yeager, Meredith;Zhou, Weiyin;Wacholder, Sholom;Wang, Zhaoming;Rodriguez-Santiago, Benjamin;Hutchinson, Amy;Deng, Xiang;Liu, Chenwei;Horner, Marie-Josephe;Cullen, Michael;Epstein, Caroline G.;Burdett, Laurie;Dean, Michael C.;Chatterjee, Nilanjan;Sampson, Joshua;Chung, Charles C.;Kovaks, Joseph;Gapstur, Susan M.;Stevens, Victoria L.;Teras, Lauren T.;Gaudet, Mia M.;Albanes, Demetrius;Weinstein, Stephanie J.;Virtamo, Jarmo;Taylor, Philip R.;Freedman, Neal D.;Abnet, Christian C.;Goldstein, Alisa M.;Hu, Nan;Yu, Kai;Yuan, Jian-Min;Liao, Linda;Ding, Ti;Qiao, You-Lin;Gao, Yu-Tang;Koh, Woon-Puay;Xiang, Yong-Bing;Tang, Ze-Zhong;Fan, Jin-Hu;Aldrich, Melinda C.;Amos, Christopher;Blot, William J.;Bock, Cathryn H.;Gillanders, Elizabeth M.;Harris, Curtis C.;Haiman, Christopher A.;Henderson, Brian E.;Kolonel, Laurence N.;Le Marchand, Loic;McNeill, Lorna H.;Rybicki, Benjamin A.;Schwartz, Ann G.;Signorello, Lisa B.;Spitz, Margaret R.;Wiencke, John K.;Wrensch, Margaret;Wu, Xifeng;Zanetti, Krista A.;Ziegler, Regina G.;Figueroa, Jonine D.;Garcia-Closas, Montserrat;Malats, Nuria;Marenne, Gaelle;Prokunina-Olsson, Ludmila;Baris, Dalsu;Schwenn, Molly;Johnson, Alison;Landi, Maria Teresa;Goldin, Lynn;Consonni, Dario;Bertazzi, Pier Alberto;Rotunno, Melissa;Rajaraman, Preetha;Andersson, Ulrika;Freeman, Laura E. Beane;Berg, Christine D.;Buring, Julie E.;Butler, Mary A.;Carreon, Tania;Feychting, Maria;Ahlbom, Anders;Gaziano, J. Michael;Giles, Graham G.;Hallmans, Goran;Hankinson, Susan E.;Hartge, Patricia;Henriksson, Roger;Inskip, Peter D.;Johansen, Christoffer;Landgren, Annelie;McKean-Cowdin, Roberta;Michaud, Dominique S.;Melin, Beatrice S.;Peters, Ulrike;Ruder, Avima M.;Sesso, Howard D.;Severi, Gianluca;Shu, Xiao-Ou;Visvanathan, Kala;White, Emily;Wolk, Alicja;Zeleniuch-Jacquotte, Anne;Zheng, Wei;Silverman, Debra T.;Kogevinas, Manolis;Gonzalez, Juan R.;Villa, Olaya;Li, Donghui;Duell, Eric J.;Risch, Harvey A.;Olson, Sara H.;Kooperberg, Charles;Wolpin, Brian M.;Jiao, Li;Hassan, Manal;Wheeler, William;Arslan, Alan A.;Bueno-de-Mesquita, H. Bas;Fuchs, Charles S.;Gallinger, Steven;Gross, Myron D.;Holly, Elizabeth A.;Klein, Alison P.;LaCroix, Andrea;Mandelson, Margaret T.;Petersen, Gloria;Boutron-Ruault, Marie-Christine;Bracci, Paige M.;Canzian, Federico;Chang, Kenneth;Cotterchio, Michelle;Giovannucci, Edward L.;Goggins, Michael;Bolton, Judith A. Hoffman;Jenab, Mazda;Khaw, Kay-Tee;Krogh, Vittorio;Kurtz, Robert C.;McWilliams, Robert R.;Mendelsohn, Julie B.;Rabe, Kari G.;Riboli, Elio;Tjonneland, Anne;Tobias, Geoffrey S.;Trichopoulos, Dimitrios;Elena, Joanne W.;Yu, Herbert;Amundadottir, Laufey;Stolzenberg-Solomon, Rachael Z.;Kraft, Peter;Schumacher, Fredrick;Stram, Daniel;Savage, Sharon A.;Mirabello, Lisa;Andrulis, Irene L.;Wunder, Jay S.;Patino Garcia, Ana;Sierrasesumaga, Luis;Barkauskas, Donald A.;Gorlick, Richard G.;Purdue, Mark;Chow, Wong-Ho;Moore, Lee E.;Schwartz, Kendra L.;Davis, Faith G.;Hsing, Ann W.;Berndt, Sonja I.;Black, Amanda;Wentzensen, Nicolas;Brinton, Louise A.;Lissowska, Jolanta;Peplonska, Beata;McGlynn, Katherine A.;Cook, Michael B.;Graubard, Barry I.;Kratz, Christian P.;Greene, Mark H.;Erickson, Ralph L.;Hunter, David J.;Thomas, Gilles;Hoover, Robert N.;Real, Francisco X.;Fraumeni, Joseph F., Jr.;Caporaso, Neil E.;Tucker, Margaret;Rothman, Nathaniel;Perez-Jurado, Luis A.;Chanock, Stephen J.
通讯作者：
Chanock, Stephen J.