A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

被引：461

作者：

Berger, Ashton C. ^{[1
,3
]}

Korkut, Anil ^{[2
]}

Kanchi, Rupa S. ^{[2
]}

Hegde, Apurva M. ^{[2
]}

Lenoir, Walter ^{[2
]}

Liu, Wenbin ^{[2
]}

Liu, Yuexin ^{[2
]}

Fan, Huihui ^{[3
]}

Shen, Hui ^{[3
]}

Ravikumar, Visweswaran ^{[2
]}

Rao, Arvind ^{[2
]}

Schultz, Andre ^{[2
]}

Li, Xubin ^{[2
]}

Sumazin, Pavel ^{[4
]}

Williams, Cecilia ^{[5
]}

Mestdagh, Pieter ^{[6
]}

Gunaratne, Preethi H. ^{[7
,8
]}

Yau, Christina ^{[9
,10
]}

Bowlby, Reanne ^{[11
]}

Robertson, A. Gordon ^{[11
]}

Tiezzi, Daniel G. ^{[12
]}

Wang, Chen ^{[13
,14
]}

Cherniack, Andrew D. ^{[1
,15
]}

Godwin, Andrew K. ^{[16
]}

Kuderer, Nicole M. ^{[17
,18
]}

Rader, Janet S. ^{[19
]}

Zuna, Rosemary E. ^{[20
]}

Sood, Anil K. ^{[21
]}

Lazar, Alexander J. ^{[22
,23
,24
]}

Ojesina, Akinyemi I. ^{[25
,26
]}

Adebamowo, Clement ^{[27
,28
,29
]}

Adebamowo, Sally N. ^{[27
,28
]}

Baggerly, Keith A. ^{[2
]}

Chen, Ting-Wen ^{[4
,30
]}

Chiu, Hua-Sheng ^{[4
]}

Lefever, Steve ^{[6
]}

Liu, Liang ^{[31
]}

MacKenzie, Karen ^{[32
]}

Orsulic, Sandra ^{[33
]}

Roszik, Jason ^{[34
]}

Shelley, Carl Simon ^{[35
]}

Song, Qianqian ^{[31
]}

Vellano, Christopher P. ^{[36
]}

Wentzensen, Nicolas ^{[37
]}

Weinstein, John N. ^{[2
,36
]}

Mills, Gordon B. ^{[36
]}

Levine, Douglas A. ^{[38
]}

Akbani, Rehan ^{[2
]}

机构：

[1] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[3] Van Andel Res Inst, Ctr Epigenet, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA

[4] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[5] KTH Royal Inst Technol, Sci Life Lab, Dept Prot Sci, CBH, Tomtebodavagen 23, S-17121 Solna, Sweden

[6] Univ Ghent, Dept Pediat & Med Genet, Ghent, Belgium

[7] Univ Houston, UH Sequencing Core, Dept Biol & Biochem, Houston, TX 77204 USA

[8] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[9] Buck Inst Res Aging, Novato, CA 94945 USA

[10] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA

[11] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada

[12] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Breast Dis & Gynecol Oncol Div, BR-14048900 Ribeirao Preto, SP, Brazil

[13] Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA

[14] Mayo Clin, Coll Med, Dept Obstet & Gynecol, 200 First St SW, Rochester, MN 55905 USA

[15] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[16] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USA

[17] Adv Canc Res Grp, Seattle, WA USA

[18] Univ Washington, Dept Med, Ctr Canc Innovat, Seattle, WA 98195 USA

[19] Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA

[20] Univ Oklahoma, Hlth Sci Ctr, Pathol Dept, Oklahoma City, OK 73104 USA

[21] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA

[22] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[23] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[24] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[25] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA

[26] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA

[27] Univ Maryland, Sch Med, Inst Human Virol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA

[28] Univ Maryland, Sch Med, Greenebaum Comprehens Canc Ctr, Baltimore, MD 21201 USA

[29] Inst Human Virol, Abuja, Nigeria

[30] Chang Gung Univ, Mol Med Res Ctr, Bioinformat Ctr, Taoyuan, Taiwan

[31] Wake Forest Baptist Hlth Ctr, Dept Canc Biol, Winston Salem, NC 27157 USA

[32] Univ New South Wales, Sch Womens & Childrens Hlth, Sydney, NSW, Australia

[33] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA

[34] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[35] Leukemia Therapeut LLC, Hull, MA 02045 USA

[36] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[37] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[38] New York Univ Langone Hlth, Perlmutter Canc Ctr, Gynecol Oncol, New York, NY 10016 USA

来源：

CANCER CELL | 2018年 / 33卷 / 04期

关键词：

MUTATIONAL SIGNATURES; CLASS DISCOVERY; MICROARRAY; GENERATION; LANDSCAPE; ACCURATE; REVEALS; PFKFB3; QUANTIFICATION; IDENTIFICATION;

D O I：

10.1016/j.ccell.2018.03.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.

引用

页码：690 / +

页数：25

共 75 条

[1] A pan-cancer proteomic perspective on The Cancer Genome Atlas [J].

Akbani, Rehan ;

Ng, Patrick Kwok Shing ;

Werner, Henrica M. J. ;

Shahmoradgoli, Maria ;

Zhang, Fan ;

Ju, Zhenlin ;

Liu, Wenbin ;

Yang, Ji-Yeon ;

Yoshihara, Kosuke ;

Li, Jun ;

Ling, Shiyun ;

Seviour, Elena G. ;

Ram, Prahlad T. ;

Minna, John D. ;

Diao, Lixia ;

Tong, Pan ;

Heymach, John V. ;

Hill, Steven M. ;

Dondelinger, Frank ;

Stadler, Nicolas ;

Byers, Lauren A. ;

Meric-Bernstam, Funda ;

Weinstein, John N. ;

Broom, Bradley M. ;

Verhaak, Roeland G. W. ;

Liang, Han ;

Mukherjee, Sach ;

Lu, Yiling ;

Mills, Gordon B. .

NATURE COMMUNICATIONS, 2014, 5

[2] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[3] Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].

Altschul, SF ;

Madden, TL ;

Schaffer, AA ;

Zhang, JH ;

Zhang, Z ;

Miller, W ;

Lipman, DJ .

NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402

[4] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[5] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[6] Integrated genomic and molecular characterization of cervical cancer [J].

Burk, Robert D. ;

Chen, Zigui ;

Saller, Charles ;

Tarvin, Katherine ;

Carvalho, Andre L. ;

Scapulatempo-Neto, Cristovam ;

Silveira, Henrique C. ;

Fregnani, Jose H. ;

Creighton, Chad J. ;

Anderson, Matthew L. ;

Castro, Patricia ;

Wang, Sophia S. ;

Yau, Christina ;

Benz, Christopher ;

Robertson, A. Gordon ;

Mungall, Karen ;

Lim, Lynette ;

Bowlby, Reanne ;

Sadeghi, Sara ;

Brooks, Denise ;

Sipahimalani, Payal ;

Mar, Richard ;

Ally, Adrian ;

Clarke, Amanda ;

Mungall, Andrew J. ;

Tam, Angela ;

Lee, Darlene ;

Chuah, Eric ;

Schein, Jacqueline E. ;

Tse, Kane ;

Kasaian, Katayoon ;

Ma, Yussanne ;

Marra, Marco A. ;

Mayo, Michael ;

Balasundaram, Miruna ;

Thiessen, Nina ;

Dhalla, Noreen ;

Carlsen, Rebecca ;

Moore, Richard A. ;

Holt, Robert A. ;

Jones, Steven J. M. ;

Wong, Tina ;

Pantazi, Angeliki ;

Parfenov, Michael ;

Kucherlapati, Raju ;

Hadjipanayis, Angela ;

Seidman, Jonathan ;

Kucherlapati, Melanie ;

Ren, Xiaojia ;

Xu, Andrew W. .

NATURE, 2017, 543 (7645) :378-+

[7] Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy [J].

Cantelmo, Anna Rita ;

Conradi, Lena-Christin ;

Brajic, Aleksandra ;

Goveia, Jermaine ;

Kalucka, Joanna ;

Pircher, Andreas ;

Chaturvedi, Pallavi ;

Hol, Johanna ;

Thienpont, Bernard ;

Teuwen, Laure-Anne ;

Schoors, Sandra ;

Boeckx, Bram ;

Vriens, Joris ;

Kuchnio, Anna ;

Veys, Koen ;

Cruys, Bert ;

Finotto, Lise ;

Treps, Lucas ;

Stav-Noraas, Tor Espen ;

Bifari, Francesco ;

Stapor, Peter ;

Decimo, Ilaria ;

Kampen, Kim ;

De Bock, Katrien ;

Haraldsen, Guttorm ;

Schoonjans, Luc ;

Rabelink, Ton ;

Eelen, Guy ;

Ghesquiere, Bart ;

Rehman, Jalees ;

Lambrechts, Diether ;

Malik, Asrar B. ;

Dewerchin, Mieke ;

Carmeliet, Peter .

CANCER CELL, 2016, 30 (06) :968-985

[8] Absolute quantification of somatic DNA alterations in human cancer [J].

Carter, Scott L. ;

Cibulskis, Kristian ;

Helman, Elena ;

McKenna, Aaron ;

Shen, Hui ;

Zack, Travis ;

Laird, Peter W. ;

Onofrio, Robert C. ;

Winckler, Wendy ;

Weir, Barbara A. ;

Beroukhim, Rameen ;

Pellman, David ;

Levine, Douglas A. ;

Lander, Eric S. ;

Meyerson, Matthew ;

Getz, Gad .

NATURE BIOTECHNOLOGY, 2012, 30 (05) :413-+

[9] Integrated Molecular Characterization of Uterine Carcinosarcoma [J].

Cherniack, Andrew D. ;

Shen, Hui ;

Walter, Vonn ;

Stewart, Chip ;

Murray, Bradley A. ;

Bowlby, Reanne ;

Hu, Xin ;

Ling, Shiyun ;

Soslow, Robert A. ;

Broaddus, Russell R. ;

Zuna, Rosemary E. ;

Robertson, Gordon ;

Laird, Peter W. ;

Kucherlapati, Raju ;

Mills, Gordon B. ;

Weinstein, John N. ;

Zhang, Jiashan ;

Akbani, Rehan ;

Levine, Douglas A. .

CANCER CELL, 2017, 31 (03) :411-423

[10] Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context [J].

Chiu, Hua-Sheng ;

Somvanshi, Sonal ;

Patel, Ektaben ;

Chen, Ting-Wen ;

Singh, Vivek P. ;

Zorman, Barry ;

Patil, Sagar L. ;

Pan, Yinghong ;

Chatterjee, Sujash S. ;

Sood, Anil K. ;

Gunaratne, Preethi H. ;

Sumazin, Pavel .

CELL REPORTS, 2018, 23 (01) :297-+

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