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Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.
Cancer Cell ( IF 50.3 ) Pub Date : 2017-08-14 , DOI: 10.1016/j.ccell.2017.07.007 Benjamin J. Raphael , Ralph H. Hruban , Andrew J. Aguirre , Richard A. Moffitt , Jen Jen Yeh , Chip Stewart , A. Gordon Robertson , Andrew D. Cherniack , Manaswi Gupta , Gad Getz , Stacey B. Gabriel , Matthew Meyerson , Carrie Cibulskis , Suzanne S. Fei , Toshinori Hinoue , Hui Shen , Peter W. Laird , Shiyun Ling , Yiling Lu , Gordon B. Mills , Rehan Akbani , Phillipe Loher , Eric R. Londin , Isidore Rigoutsos , Aristeidis G. Telonis , Ewan A. Gibb , Anna Goldenberg , Aziz M. Mezlini , Katherine A. Hoadley , Eric Collisson , Eric Lander , Bradley A. Murray , Julian Hess , Mara Rosenberg , Louis Bergelson , Hailei Zhang , Juok Cho , Grace Tiao , Jaegil Kim , Dimitri Livitz , Ignaty Leshchiner , Brendan Reardon , Eliezer Van Allen , Atanas Kamburov , Rameen Beroukhim , Gordon Saksena , Steven E. Schumacher , Michael S. Noble , David I. Heiman , Nils Gehlenborg , Jaegil Kim , Michael S. Lawrence , Volkan Adsay , Gloria Petersen , David Klimstra , Nabeel Bardeesy , Mark D.M. Leiserson , Reanne Bowlby , Katayoon Kasaian , Inanc Birol , Karen L. Mungall , Sara Sadeghi , John N. Weinstein , Paul T. Spellman , Yuexin Liu , Laufey T. Amundadottir , Joel Tepper , Aatur D. Singhi , Rajiv Dhir , Drwiega Paul , Thomas Smyrk , Lizhi Zhang , Paula Kim , Jay Bowen , Jessica Frick , Julie M. Gastier-Foster , Mark Gerken , Kevin Lau , Kristen M. Leraas , Tara M. Lichtenberg , Nilsa C. Ramirez , Jeremy Renkel , Mark Sherman , Lisa Wise , Peggy Yena , Erik Zmuda , Juliann Shih , Adrian Ally , Miruna Balasundaram , Rebecca Carlsen , Andy Chu , Eric Chuah , Amanda Clarke , Noreen Dhalla , Robert A. Holt , Steven J.M. Jones , Darlene Lee , Yussanne Ma , Marco A. Marra , Michael Mayo , Richard A. Moore , Andrew J. Mungall , Jacqueline E. Schein , Payal Sipahimalani , Angela Tam , Nina Thiessen , Kane Tse , Tina Wong , Denise Brooks , J. Todd Auman , Saianand Balu , Tom Bodenheimer , D. Neil Hayes , Alan P. Hoyle , Stuart R. Jefferys , Corbin D. Jones , Shaowu Meng , Piotr A. Mieczkowski , Lisle E. Mose , Charles M. Perou , Amy H. Perou , Jeffrey Roach , Yan Shi , Janae V. Simons , Tara Skelly , Matthew G. Soloway , Donghui Tan , Umadevi Veluvolu , Joel S. Parker , Matthew D. Wilkerson , Anil Korkut , Yasin Senbabaoglu , Patrick Burch , Robert McWilliams , Kari Chaffee , Ann Oberg , Wei Zhang , Marie-Claude Gingras , David A. Wheeler , Liu Xi , Monique Albert , John Bartlett , Harman Sekhon , Yeager Stephen , Zaren Howard , Miller Judy , Anne Breggia , Rachna T. Shroff , Sudha Chudamani , Jia Liu , Laxmi Lolla , Rashi Naresh , Todd Pihl , Qiang Sun , Yunhu Wan , Ye Wu , Smith Jennifer , Kevin Roggin , Karl-Friedrich Becker , Madhusmita Behera , Joseph Bennett , Lori Boice , Eric Burks , Carlos Gilberto Carlotti Junior , John Chabot , Daniela Pretti da Cunha Tirapelli , Jose Sebastião dos Santos , Michael Dubina , Jennifer Eschbacher , Mei Huang , Lori Huelsenbeck-Dill , Roger Jenkins , Alexey Karpov , Rafael Kemp , Vladimir Lyadov , Shishir Maithel , Georgy Manikhas , Eric Montgomery , Houtan Noushmehr , Adeboye Osunkoya , Taofeek Owonikoko , Oxana Paklina , Olga Potapova , Suresh Ramalingam , W. Kimryn Rathmell , Kimberly Rieger-Christ , Charles Saller , Galiya Setdikova , Alexey Shabunin , Gabriel Sica , Tao Su , Travis Sullivan , Pat Swanson , Katherine Tarvin , Michael Tavobilov , Leigh B. Thorne , Stefan Urbanski , Olga Voronina , Timothy Wang , Daniel Crain , Erin Curley , Johanna Gardner , David Mallery , Scott Morris , Joseph Paulauskis , Robert Penny , Candace Shelton , Troy Shelton , Klaus-Peter Janssen , Oliver Bathe , Nathan Bahary , Julia Slotta-Huspenina , Amber Johns , Hanina Hibshoosh , Rosa F. Hwang , Antonia Sepulveda , Amie Radenbaugh , Stephen B. Baylin , Mario Berrios , Moiz S. Bootwalla , Andrea Holbrook , Phillip H. Lai , Dennis T. Maglinte , Swapna Mahurkar , Timothy J. Triche , David J. Van Den Berg , Daniel J. Weisenberger , Lynda Chin , Raju Kucherlapati , Melanie Kucherlapati , Angeliki Pantazi , Peter Park , Gordon Saksena , Doug Voet , Pei Lin , Scott Frazer , Timothy Defreitas , Sam Meier , Lynda Chin , Sun Young Kwon , Yong Hoon Kim , Sang-Jae Park , Sung-Sik Han , Seong Hoon Kim , Hark Kim , Emma Furth , Margaret Tempero , Chris Sander , Andrew Biankin , David Chang , Peter Bailey , Anthony Gill , James Kench , Sean Grimmond , Amber Johns , Australian Pancreatic Cancer Genome Initiative (APGI , Russell Postier , Rosemary Zuna , Hugues Sicotte , John A. Demchok , Martin L. Ferguson , Carolyn M. Hutter , Kenna R. Mills Shaw , Margi Sheth , Heidi J. Sofia , Roy Tarnuzzer , Zhining Wang , Liming Yang , Jiashan (Julia) Zhang , Ina Felau , Jean C. Zenklusen
Cancer Cell ( IF 50.3 ) Pub Date : 2017-08-14 , DOI: 10.1016/j.ccell.2017.07.007 Benjamin J. Raphael , Ralph H. Hruban , Andrew J. Aguirre , Richard A. Moffitt , Jen Jen Yeh , Chip Stewart , A. Gordon Robertson , Andrew D. Cherniack , Manaswi Gupta , Gad Getz , Stacey B. Gabriel , Matthew Meyerson , Carrie Cibulskis , Suzanne S. Fei , Toshinori Hinoue , Hui Shen , Peter W. Laird , Shiyun Ling , Yiling Lu , Gordon B. Mills , Rehan Akbani , Phillipe Loher , Eric R. Londin , Isidore Rigoutsos , Aristeidis G. Telonis , Ewan A. Gibb , Anna Goldenberg , Aziz M. Mezlini , Katherine A. Hoadley , Eric Collisson , Eric Lander , Bradley A. Murray , Julian Hess , Mara Rosenberg , Louis Bergelson , Hailei Zhang , Juok Cho , Grace Tiao , Jaegil Kim , Dimitri Livitz , Ignaty Leshchiner , Brendan Reardon , Eliezer Van Allen , Atanas Kamburov , Rameen Beroukhim , Gordon Saksena , Steven E. Schumacher , Michael S. Noble , David I. Heiman , Nils Gehlenborg , Jaegil Kim , Michael S. Lawrence , Volkan Adsay , Gloria Petersen , David Klimstra , Nabeel Bardeesy , Mark D.M. Leiserson , Reanne Bowlby , Katayoon Kasaian , Inanc Birol , Karen L. Mungall , Sara Sadeghi , John N. Weinstein , Paul T. Spellman , Yuexin Liu , Laufey T. Amundadottir , Joel Tepper , Aatur D. Singhi , Rajiv Dhir , Drwiega Paul , Thomas Smyrk , Lizhi Zhang , Paula Kim , Jay Bowen , Jessica Frick , Julie M. Gastier-Foster , Mark Gerken , Kevin Lau , Kristen M. Leraas , Tara M. Lichtenberg , Nilsa C. Ramirez , Jeremy Renkel , Mark Sherman , Lisa Wise , Peggy Yena , Erik Zmuda , Juliann Shih , Adrian Ally , Miruna Balasundaram , Rebecca Carlsen , Andy Chu , Eric Chuah , Amanda Clarke , Noreen Dhalla , Robert A. Holt , Steven J.M. Jones , Darlene Lee , Yussanne Ma , Marco A. Marra , Michael Mayo , Richard A. Moore , Andrew J. Mungall , Jacqueline E. Schein , Payal Sipahimalani , Angela Tam , Nina Thiessen , Kane Tse , Tina Wong , Denise Brooks , J. Todd Auman , Saianand Balu , Tom Bodenheimer , D. Neil Hayes , Alan P. Hoyle , Stuart R. Jefferys , Corbin D. Jones , Shaowu Meng , Piotr A. Mieczkowski , Lisle E. Mose , Charles M. Perou , Amy H. Perou , Jeffrey Roach , Yan Shi , Janae V. Simons , Tara Skelly , Matthew G. Soloway , Donghui Tan , Umadevi Veluvolu , Joel S. Parker , Matthew D. Wilkerson , Anil Korkut , Yasin Senbabaoglu , Patrick Burch , Robert McWilliams , Kari Chaffee , Ann Oberg , Wei Zhang , Marie-Claude Gingras , David A. Wheeler , Liu Xi , Monique Albert , John Bartlett , Harman Sekhon , Yeager Stephen , Zaren Howard , Miller Judy , Anne Breggia , Rachna T. Shroff , Sudha Chudamani , Jia Liu , Laxmi Lolla , Rashi Naresh , Todd Pihl , Qiang Sun , Yunhu Wan , Ye Wu , Smith Jennifer , Kevin Roggin , Karl-Friedrich Becker , Madhusmita Behera , Joseph Bennett , Lori Boice , Eric Burks , Carlos Gilberto Carlotti Junior , John Chabot , Daniela Pretti da Cunha Tirapelli , Jose Sebastião dos Santos , Michael Dubina , Jennifer Eschbacher , Mei Huang , Lori Huelsenbeck-Dill , Roger Jenkins , Alexey Karpov , Rafael Kemp , Vladimir Lyadov , Shishir Maithel , Georgy Manikhas , Eric Montgomery , Houtan Noushmehr , Adeboye Osunkoya , Taofeek Owonikoko , Oxana Paklina , Olga Potapova , Suresh Ramalingam , W. Kimryn Rathmell , Kimberly Rieger-Christ , Charles Saller , Galiya Setdikova , Alexey Shabunin , Gabriel Sica , Tao Su , Travis Sullivan , Pat Swanson , Katherine Tarvin , Michael Tavobilov , Leigh B. Thorne , Stefan Urbanski , Olga Voronina , Timothy Wang , Daniel Crain , Erin Curley , Johanna Gardner , David Mallery , Scott Morris , Joseph Paulauskis , Robert Penny , Candace Shelton , Troy Shelton , Klaus-Peter Janssen , Oliver Bathe , Nathan Bahary , Julia Slotta-Huspenina , Amber Johns , Hanina Hibshoosh , Rosa F. Hwang , Antonia Sepulveda , Amie Radenbaugh , Stephen B. Baylin , Mario Berrios , Moiz S. Bootwalla , Andrea Holbrook , Phillip H. Lai , Dennis T. Maglinte , Swapna Mahurkar , Timothy J. Triche , David J. Van Den Berg , Daniel J. Weisenberger , Lynda Chin , Raju Kucherlapati , Melanie Kucherlapati , Angeliki Pantazi , Peter Park , Gordon Saksena , Doug Voet , Pei Lin , Scott Frazer , Timothy Defreitas , Sam Meier , Lynda Chin , Sun Young Kwon , Yong Hoon Kim , Sang-Jae Park , Sung-Sik Han , Seong Hoon Kim , Hark Kim , Emma Furth , Margaret Tempero , Chris Sander , Andrew Biankin , David Chang , Peter Bailey , Anthony Gill , James Kench , Sean Grimmond , Amber Johns , Australian Pancreatic Cancer Genome Initiative (APGI , Russell Postier , Rosemary Zuna , Hugues Sicotte , John A. Demchok , Martin L. Ferguson , Carolyn M. Hutter , Kenna R. Mills Shaw , Margi Sheth , Heidi J. Sofia , Roy Tarnuzzer , Zhining Wang , Liming Yang , Jiashan (Julia) Zhang , Ina Felau , Jean C. Zenklusen
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We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.
中文翻译：
胰腺导管腺癌的综合基因组学表征。
我们对150例胰腺导管腺癌（PDAC）标本进行了基因组，转录组和蛋白质组学分析，包括具有低肿瘤细胞特征的标本。深入的全外显子组测序揭示了KRAS，TP53，CDKN2A，SMAD4，RNF43，ARID1A，TGFβR2，GNAS，RREB1和PBRM1中的复发性体细胞突变。KRAS野生型肿瘤在其他致癌驱动因子（包括GNAS，BRAF，CTNNB1和其他RAS途径基因）中具有改变。一部分肿瘤具有多个KRAS突变，其中一些显示出双等位基因突变的证据。蛋白质谱分析确定了良好的预后亚型，具有低的上皮-间质转化和高的MTOR通路评分。还确定了非编码RNA与肿瘤特异性mRNA亚型的关联。
更新日期：2017-08-14
中文翻译：
胰腺导管腺癌的综合基因组学表征。
我们对150例胰腺导管腺癌（PDAC）标本进行了基因组，转录组和蛋白质组学分析，包括具有低肿瘤细胞特征的标本。深入的全外显子组测序揭示了KRAS，TP53，CDKN2A，SMAD4，RNF43，ARID1A，TGFβR2，GNAS，RREB1和PBRM1中的复发性体细胞突变。KRAS野生型肿瘤在其他致癌驱动因子（包括GNAS，BRAF，CTNNB1和其他RAS途径基因）中具有改变。一部分肿瘤具有多个KRAS突变，其中一些显示出双等位基因突变的证据。蛋白质谱分析确定了良好的预后亚型，具有低的上皮-间质转化和高的MTOR通路评分。还确定了非编码RNA与肿瘤特异性mRNA亚型的关联。
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