Integrated Molecular Characterization of Uterine Carcinosarcoma

Andrew D. Cherniack; Hui Shen; Vonn Walter; Chip Stewart; Bradley A. Murray; Reanne Bowlby; Xin Hu; Shiyun Ling; Robert A. Soslow; Russell R. Broaddus; Rosemary E. Zuna; Gordon Robertson; Peter W. Laird; Raju Kucherlapati; Gordon B. Mills; Rehan Akbani; Adrian Ally; J. Todd Auman; Miruna Balasundaram; Saianand Balu; Stephen B. Baylin; Rameen Beroukhim; Tom Bodenheimer; Faina Bogomolniy; Lori Boice; Moiz S. Bootwalla; Jay Bowen; Reanne Bowlby; Russell Broaddus; Denise Brooks; Rebecca Carlsen; Andrew D. Cherniack; Juok Cho; Eric Chuah; Sudha Chudamani; Kristian Cibulskis; Melissa Cline; Fanny Dao; Mutch David; John A. Demchok; Noreen Dhalla; Sean Dowdy; Ina Felau; Martin L. Ferguson; Scott Frazer; Jessica Frick; Stacey Gabriel; Julie M. Gastier-Foster; Nils Gehlenborg; Mark Gerken; Gad Getz; Manaswi Gupta; David Haussler; D. Neil Hayes; David I. Heiman; Julian Hess; Katherine A. Hoadley; Robert Hoffmann; Robert A. Holt; Alan P. Hoyle; Xin Hu; Mei Huang; Carolyn M. Hutter; Stuart R. Jefferys; Steven J.M. Jones; Corbin D. Jones; Rupa S. Kanchi; Cyriac Kandoth; Katayoon Kasaian; Sarah Kerr; Jaegil Kim; Phillip H. Lai; Peter W. Laird; Eric Lander; Michael S. Lawrence; Darlene Lee; Kristen M. Leraas; Ignaty Leshchiner; Douglas A. Levine; Tara M. Lichtenberg; Pei Lin; Shiyun Ling; Jia Liu; Wenbin Liu; Yuexin Liu; Laxmi Lolla; Yiling Lu; Yussanne Ma; Dennis T. Maglinte; Marco A. Marra; Michael Mayo; Shaowu Meng; Matthew Meyerson; Piotr A. Mieczkowski; Gordon B. Mills; Richard A. Moore; Lisle E. Mose; Andrew J. Mungall; Karen Mungall; Bradley A. Murray; Rashi Naresh; Michael S. Noble; Narciso Olvera; Joel S. Parker; Charles M. Perou; Amy H. Perou; Todd Pihl; Amie J. Radenbaugh; Nilsa C. Ramirez; W. Kimryn Rathmell; Jeffrey Roach; A. Gordon Robertson; Sara Sadeghi; Gordon Saksena; Helga B. Salvesen; Jacqueline E. Schein; Steven E. Schumacher; Hui Shen; Margi Sheth; Yan Shi; Juliann Shih; Janae V. Simons; Payal Sipahimalani; Tara Skelly; Heidi J. Sofia; Matthew G. Soloway; Robert A. Soslow; Carrie Sougnez; Chip Stewart; Charlie Sun; Angela Tam; Donghui Tan; Roy Tarnuzzer; Nina Thiessen; Leigh B. Thorne; Kane Tse; Jill Tseng; David J. Van Den Berg; Umadevi Veluvolu; Roel G.W. Verhaak; Doug Voet; Amanda von Bismarck; Vonn Walter; Yunhu Wan; Zhining Wang; Chen Wang; John N. Weinstein; Daniel J. Weisenberger; Matthew D. Wilkerson; Boris Winterhoff; Lisa Wise; Tina Wong; Ye Wu; Liming Yang; Jean C. Zenklusen; Jiashan (Julia) Zhang; Hailei Zhang; Wei Zhang; Jing chun Zhu; Erik Zmuda; Rosemary E. Zuna; John N. Weinstein; Jiashan Zhang; Rehan Akbani; Douglas A. Levine

doi:10.1016/j.ccell.2017.02.010

Integrated Molecular Characterization of Uterine Carcinosarcoma

Andrew D. Cherniack, Hui Shen, Vonn Walter, Chip Stewart, Bradley A. Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert A. Soslow, Russell R. Broaddus, Rosemary E. Zuna, Gordon Robertson, Peter W. Laird, Raju Kucherlapati, Gordon B. Mills, Rehan Akbani, Adrian Ally, J. Todd Auman, Miruna Balasundaram, Saianand BaluStephen B. Baylin, Rameen Beroukhim, Tom Bodenheimer, Faina Bogomolniy, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Reanne Bowlby, Russell Broaddus, Denise Brooks, Rebecca Carlsen, Andrew D. Cherniack, Juok Cho, Eric Chuah, Sudha Chudamani, Kristian Cibulskis, Melissa Cline, Fanny Dao, Mutch David, John A. Demchok, Noreen Dhalla, Sean Dowdy, Ina Felau, Martin L. Ferguson, Scott Frazer, Jessica Frick, Stacey Gabriel, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, Manaswi Gupta, David Haussler, D. Neil Hayes, David I. Heiman, Julian Hess, Katherine A. Hoadley, Robert Hoffmann, Robert A. Holt, Alan P. Hoyle, Xin Hu, Mei Huang, Carolyn M. Hutter, Stuart R. Jefferys, Steven J.M. Jones, Corbin D. Jones, Rupa S. Kanchi, Cyriac Kandoth, Katayoon Kasaian, Sarah Kerr, Jaegil Kim, Phillip H. Lai, Peter W. Laird, Eric Lander, Michael S. Lawrence, Darlene Lee, Kristen M. Leraas, Ignaty Leshchiner, Douglas A. Levine, Tara M. Lichtenberg, Pei Lin, Shiyun Ling, Jia Liu, Wenbin Liu, Yuexin Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, Marco A. Marra, Michael Mayo, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Gordon B. Mills, Richard A. Moore, Lisle E. Mose, Andrew J. Mungall, Karen Mungall, Bradley A. Murray, Rashi Naresh, Michael S. Noble, Narciso Olvera, Joel S. Parker, Charles M. Perou, Amy H. Perou, Todd Pihl, Amie J. Radenbaugh, Nilsa C. Ramirez, W. Kimryn Rathmell, Jeffrey Roach, A. Gordon Robertson, Sara Sadeghi, Gordon Saksena, Helga B. Salvesen, Jacqueline E. Schein, Steven E. Schumacher, Hui Shen, Margi Sheth, Yan Shi, Juliann Shih, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Robert A. Soslow, Carrie Sougnez, Chip Stewart, Charlie Sun, Angela Tam, Donghui Tan, Roy Tarnuzzer, Nina Thiessen, Leigh B. Thorne, Kane Tse, Jill Tseng, David J. Van Den Berg, Umadevi Veluvolu, Roel G.W. Verhaak, Doug Voet, Amanda von Bismarck, Vonn Walter, Yunhu Wan, Zhining Wang, Chen Wang, John N. Weinstein, Daniel J. Weisenberger, Matthew D. Wilkerson, Boris Winterhoff, Lisa Wise, Tina Wong, Ye Wu, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Hailei Zhang, Wei Zhang, Jing chun Zhu, Erik Zmuda, Rosemary E. Zuna, John N. Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A. Levine

Obstetrics, Gynecology and Women's Health - Oncology

Research output: Contribution to journal › Article › peer-review

245 Scopus citations

Abstract

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Original language	English (US)
Pages (from-to)	411-423
Number of pages	13
Journal	Cancer Cell
Volume	31
Issue number	3
DOIs	https://doi.org/10.1016/j.ccell.2017.02.010
State	Published - Mar 13 2017

Bibliographical note

Funding Information:
We wish to thank all patients and families who contributed to this study. This work was supported by the following grants from the US NIH: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672. Andrew D. Cherniack and Matthew Meyerson declare research funding from Bayer AG.

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

EMT
TGGA
The Cancer Genome Atlas
UCS
endometrial cancer
epithelial-to-mesenchymal transition
gynecologic cancer
gynecologic oncology
translational science
uterine carcinosarcoma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.ccell.2017.02.010

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599133

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Cherniack, A. D., Shen, H., Walter, V., Stewart, C., Murray, B. A., Bowlby, R., Hu, X., Ling, S., Soslow, R. A., Broaddus, R. R., Zuna, R. E., Robertson, G., Laird, P. W., Kucherlapati, R., Mills, G. B., Akbani, R., Ally, A., Auman, J. T., Balasundaram, M., ... Levine, D. A. (2017). Integrated Molecular Characterization of Uterine Carcinosarcoma. Cancer Cell, 31(3), 411-423. https://doi.org/10.1016/j.ccell.2017.02.010

Cherniack, AD, Shen, H, Walter, V, Stewart, C, Murray, BA, Bowlby, R, Hu, X, Ling, S, Soslow, RA, Broaddus, RR, Zuna, RE, Robertson, G, Laird, PW, Kucherlapati, R, Mills, GB, Akbani, R, Ally, A, Auman, JT, Balasundaram, M, Balu, S, Baylin, SB, Beroukhim, R, Bodenheimer, T, Bogomolniy, F, Boice, L, Bootwalla, MS, Bowen, J, Bowlby, R, Broaddus, R, Brooks, D, Carlsen, R, Cherniack, AD, Cho, J, Chuah, E, Chudamani, S, Cibulskis, K, Cline, M, Dao, F, David, M, Demchok, JA, Dhalla, N, Dowdy, S, Felau, I, Ferguson, ML, Frazer, S, Frick, J, Gabriel, S, Gastier-Foster, JM, Gehlenborg, N, Gerken, M, Getz, G, Gupta, M, Haussler, D, Hayes, DN, Heiman, DI, Hess, J, Hoadley, KA, Hoffmann, R, Holt, RA, Hoyle, AP, Hu, X, Huang, M, Hutter, CM, Jefferys, SR, Jones, SJM, Jones, CD, Kanchi, RS, Kandoth, C, Kasaian, K, Kerr, S, Kim, J, Lai, PH, Laird, PW, Lander, E, Lawrence, MS, Lee, D, Leraas, KM, Leshchiner, I, Levine, DA, Lichtenberg, TM, Lin, P, Ling, S, Liu, J, Liu, W, Liu, Y, Lolla, L, Lu, Y, Ma, Y, Maglinte, DT, Marra, MA, Mayo, M, Meng, S, Meyerson, M, Mieczkowski, PA, Mills, GB, Moore, RA, Mose, LE, Mungall, AJ, Mungall, K, Murray, BA, Naresh, R, Noble, MS, Olvera, N, Parker, JS, Perou, CM, Perou, AH, Pihl, T, Radenbaugh, AJ, Ramirez, NC, Rathmell, WK, Roach, J, Robertson, AG, Sadeghi, S, Saksena, G, Salvesen, HB, Schein, JE, Schumacher, SE, Shen, H, Sheth, M, Shi, Y, Shih, J, Simons, JV, Sipahimalani, P, Skelly, T, Sofia, HJ, Soloway, MG, Soslow, RA, Sougnez, C, Stewart, C, Sun, C, Tam, A, Tan, D, Tarnuzzer, R, Thiessen, N, Thorne, LB, Tse, K, Tseng, J, Van Den Berg, DJ, Veluvolu, U, Verhaak, RGW, Voet, D, von Bismarck, A, Walter, V, Wan, Y, Wang, Z, Wang, C, Weinstein, JN, Weisenberger, DJ, Wilkerson, MD, Winterhoff, B, Wise, L, Wong, T, Wu, Y, Yang, L, Zenklusen, JC, Zhang, J, Zhang, H, Zhang, W, Zhu, JC, Zmuda, E, Zuna, RE, Weinstein, JN, Zhang, J, Akbani, R & Levine, DA 2017, 'Integrated Molecular Characterization of Uterine Carcinosarcoma', Cancer Cell, vol. 31, no. 3, pp. 411-423. https://doi.org/10.1016/j.ccell.2017.02.010

@article{b0d7069d1f96475d81c0e1b624b6fc19,

title = "Integrated Molecular Characterization of Uterine Carcinosarcoma",

abstract = "We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.",

keywords = "EMT, TGGA, The Cancer Genome Atlas, UCS, endometrial cancer, epithelial-to-mesenchymal transition, gynecologic cancer, gynecologic oncology, translational science, uterine carcinosarcoma",

author = "Cherniack, {Andrew D.} and Hui Shen and Vonn Walter and Chip Stewart and Murray, {Bradley A.} and Reanne Bowlby and Xin Hu and Shiyun Ling and Soslow, {Robert A.} and Broaddus, {Russell R.} and Zuna, {Rosemary E.} and Gordon Robertson and Laird, {Peter W.} and Raju Kucherlapati and Mills, {Gordon B.} and Rehan Akbani and Adrian Ally and Auman, {J. Todd} and Miruna Balasundaram and Saianand Balu and Baylin, {Stephen B.} and Rameen Beroukhim and Tom Bodenheimer and Faina Bogomolniy and Lori Boice and Bootwalla, {Moiz S.} and Jay Bowen and Reanne Bowlby and Russell Broaddus and Denise Brooks and Rebecca Carlsen and Cherniack, {Andrew D.} and Juok Cho and Eric Chuah and Sudha Chudamani and Kristian Cibulskis and Melissa Cline and Fanny Dao and Mutch David and Demchok, {John A.} and Noreen Dhalla and Sean Dowdy and Ina Felau and Ferguson, {Martin L.} and Scott Frazer and Jessica Frick and Stacey Gabriel and Gastier-Foster, {Julie M.} and Nils Gehlenborg and Mark Gerken and Gad Getz and Manaswi Gupta and David Haussler and Hayes, {D. Neil} and Heiman, {David I.} and Julian Hess and Hoadley, {Katherine A.} and Robert Hoffmann and Holt, {Robert A.} and Hoyle, {Alan P.} and Xin Hu and Mei Huang and Hutter, {Carolyn M.} and Jefferys, {Stuart R.} and Jones, {Steven J.M.} and Jones, {Corbin D.} and Kanchi, {Rupa S.} and Cyriac Kandoth and Katayoon Kasaian and Sarah Kerr and Jaegil Kim and Lai, {Phillip H.} and Laird, {Peter W.} and Eric Lander and Lawrence, {Michael S.} and Darlene Lee and Leraas, {Kristen M.} and Ignaty Leshchiner and Levine, {Douglas A.} and Lichtenberg, {Tara M.} and Pei Lin and Shiyun Ling and Jia Liu and Wenbin Liu and Yuexin Liu and Laxmi Lolla and Yiling Lu and Yussanne Ma and Maglinte, {Dennis T.} and Marra, {Marco A.} and Michael Mayo and Shaowu Meng and Matthew Meyerson and Mieczkowski, {Piotr A.} and Mills, {Gordon B.} and Moore, {Richard A.} and Mose, {Lisle E.} and Mungall, {Andrew J.} and Karen Mungall and Murray, {Bradley A.} and Rashi Naresh and Noble, {Michael S.} and Narciso Olvera and Parker, {Joel S.} and Perou, {Charles M.} and Perou, {Amy H.} and Todd Pihl and Radenbaugh, {Amie J.} and Ramirez, {Nilsa C.} and Rathmell, {W. Kimryn} and Jeffrey Roach and Robertson, {A. Gordon} and Sara Sadeghi and Gordon Saksena and Salvesen, {Helga B.} and Schein, {Jacqueline E.} and Schumacher, {Steven E.} and Hui Shen and Margi Sheth and Yan Shi and Juliann Shih and Simons, {Janae V.} and Payal Sipahimalani and Tara Skelly and Sofia, {Heidi J.} and Soloway, {Matthew G.} and Soslow, {Robert A.} and Carrie Sougnez and Chip Stewart and Charlie Sun and Angela Tam and Donghui Tan and Roy Tarnuzzer and Nina Thiessen and Thorne, {Leigh B.} and Kane Tse and Jill Tseng and {Van Den Berg}, {David J.} and Umadevi Veluvolu and Verhaak, {Roel G.W.} and Doug Voet and {von Bismarck}, Amanda and Vonn Walter and Yunhu Wan and Zhining Wang and Chen Wang and Weinstein, {John N.} and Weisenberger, {Daniel J.} and Wilkerson, {Matthew D.} and Boris Winterhoff and Lisa Wise and Tina Wong and Ye Wu and Liming Yang and Zenklusen, {Jean C.} and Zhang, {Jiashan (Julia)} and Hailei Zhang and Wei Zhang and Zhu, {Jing chun} and Erik Zmuda and Zuna, {Rosemary E.} and Weinstein, {John N.} and Jiashan Zhang and Rehan Akbani and Levine, {Douglas A.}",

note = "Funding Information: We wish to thank all patients and families who contributed to this study. This work was supported by the following grants from the US NIH: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672. Andrew D. Cherniack and Matthew Meyerson declare research funding from Bayer AG. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = mar,

day = "13",

doi = "10.1016/j.ccell.2017.02.010",

language = "English (US)",

volume = "31",

pages = "411--423",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Integrated Molecular Characterization of Uterine Carcinosarcoma

AU - Cherniack, Andrew D.

AU - Shen, Hui

AU - Walter, Vonn

AU - Stewart, Chip

AU - Murray, Bradley A.

AU - Bowlby, Reanne

AU - Hu, Xin

AU - Ling, Shiyun

AU - Soslow, Robert A.

AU - Broaddus, Russell R.

AU - Zuna, Rosemary E.

AU - Robertson, Gordon

AU - Laird, Peter W.

AU - Kucherlapati, Raju

AU - Mills, Gordon B.

AU - Akbani, Rehan

AU - Ally, Adrian

AU - Auman, J. Todd

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Baylin, Stephen B.

AU - Beroukhim, Rameen

AU - Bodenheimer, Tom

AU - Bogomolniy, Faina

AU - Boice, Lori

AU - Bootwalla, Moiz S.

AU - Bowen, Jay

AU - Bowlby, Reanne

AU - Broaddus, Russell

AU - Brooks, Denise

AU - Carlsen, Rebecca

AU - Cherniack, Andrew D.

AU - Cho, Juok

AU - Chuah, Eric

AU - Chudamani, Sudha

AU - Cibulskis, Kristian

AU - Cline, Melissa

AU - Dao, Fanny

AU - David, Mutch

AU - Demchok, John A.

AU - Dhalla, Noreen

AU - Dowdy, Sean

AU - Felau, Ina

AU - Ferguson, Martin L.

AU - Frazer, Scott

AU - Frick, Jessica

AU - Gabriel, Stacey

AU - Gastier-Foster, Julie M.

AU - Gehlenborg, Nils

AU - Gerken, Mark

AU - Getz, Gad

AU - Gupta, Manaswi

AU - Haussler, David

AU - Hayes, D. Neil

AU - Heiman, David I.

AU - Hess, Julian

AU - Hoadley, Katherine A.

AU - Hoffmann, Robert

AU - Holt, Robert A.

AU - Hoyle, Alan P.

AU - Hu, Xin

AU - Huang, Mei

AU - Hutter, Carolyn M.

AU - Jefferys, Stuart R.

AU - Jones, Steven J.M.

AU - Jones, Corbin D.

AU - Kanchi, Rupa S.

AU - Kandoth, Cyriac

AU - Kasaian, Katayoon

AU - Kerr, Sarah

AU - Kim, Jaegil

AU - Lai, Phillip H.

AU - Laird, Peter W.

AU - Lander, Eric

AU - Lawrence, Michael S.

AU - Lee, Darlene

AU - Leraas, Kristen M.

AU - Leshchiner, Ignaty

AU - Levine, Douglas A.

AU - Lichtenberg, Tara M.

AU - Lin, Pei

AU - Ling, Shiyun

AU - Liu, Jia

AU - Liu, Wenbin

AU - Liu, Yuexin

AU - Lolla, Laxmi

AU - Lu, Yiling

AU - Ma, Yussanne

AU - Maglinte, Dennis T.

AU - Marra, Marco A.

AU - Mayo, Michael

AU - Meng, Shaowu

AU - Meyerson, Matthew

AU - Mieczkowski, Piotr A.

AU - Mills, Gordon B.

AU - Moore, Richard A.

AU - Mose, Lisle E.

AU - Mungall, Andrew J.

AU - Mungall, Karen

AU - Murray, Bradley A.

AU - Naresh, Rashi

AU - Noble, Michael S.

AU - Olvera, Narciso

AU - Parker, Joel S.

AU - Perou, Charles M.

AU - Perou, Amy H.

AU - Pihl, Todd

AU - Radenbaugh, Amie J.

AU - Ramirez, Nilsa C.

AU - Rathmell, W. Kimryn

AU - Roach, Jeffrey

AU - Robertson, A. Gordon

AU - Sadeghi, Sara

AU - Saksena, Gordon

AU - Salvesen, Helga B.

AU - Schein, Jacqueline E.

AU - Schumacher, Steven E.

AU - Shen, Hui

AU - Sheth, Margi

AU - Shi, Yan

AU - Shih, Juliann

AU - Simons, Janae V.

AU - Sipahimalani, Payal

AU - Skelly, Tara

AU - Sofia, Heidi J.

AU - Soloway, Matthew G.

AU - Soslow, Robert A.

AU - Sougnez, Carrie

AU - Stewart, Chip

AU - Sun, Charlie

AU - Tam, Angela

AU - Tan, Donghui

AU - Tarnuzzer, Roy

AU - Thiessen, Nina

AU - Thorne, Leigh B.

AU - Tse, Kane

AU - Tseng, Jill

AU - Van Den Berg, David J.

AU - Veluvolu, Umadevi

AU - Verhaak, Roel G.W.

AU - Voet, Doug

AU - von Bismarck, Amanda

AU - Walter, Vonn

AU - Wan, Yunhu

AU - Wang, Zhining

AU - Wang, Chen

AU - Weinstein, John N.

AU - Weisenberger, Daniel J.

AU - Wilkerson, Matthew D.

AU - Winterhoff, Boris

AU - Wise, Lisa

AU - Wong, Tina

AU - Wu, Ye

AU - Yang, Liming

AU - Zenklusen, Jean C.

AU - Zhang, Jiashan (Julia)

AU - Zhang, Hailei

AU - Zhang, Wei

AU - Zhu, Jing chun

AU - Zmuda, Erik

AU - Zuna, Rosemary E.

AU - Weinstein, John N.

AU - Zhang, Jiashan

AU - Akbani, Rehan

AU - Levine, Douglas A.

N1 - Funding Information: We wish to thank all patients and families who contributed to this study. This work was supported by the following grants from the US NIH: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672. Andrew D. Cherniack and Matthew Meyerson declare research funding from Bayer AG. Publisher Copyright: © 2017 Elsevier Inc.

PY - 2017/3/13

Y1 - 2017/3/13

N2 - We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

AB - We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

KW - EMT

KW - TGGA

KW - The Cancer Genome Atlas

KW - UCS

KW - endometrial cancer

KW - epithelial-to-mesenchymal transition

KW - gynecologic cancer

KW - gynecologic oncology

KW - translational science

KW - uterine carcinosarcoma

UR - http://www.scopus.com/inward/record.url?scp=85015101723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015101723&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2017.02.010

DO - 10.1016/j.ccell.2017.02.010

M3 - Article

C2 - 28292439

AN - SCOPUS:85015101723

SN - 1535-6108

VL - 31

SP - 411

EP - 423

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

Integrated Molecular Characterization of Uterine Carcinosarcoma

Abstract

Bibliographical note

Keywords

UN SDGs

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