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 |
---|---|
Pages (from-to) | 411-423 |
Number of pages | 13 |
Journal | Cancer Cell |
Volume | 31 |
Issue number | 3 |
DOIs | |
State | Published - Mar 13 2017 |
Keywords
- EMT
- TGGA
- The Cancer Genome Atlas
- UCS
- endometrial cancer
- epithelial-to-mesenchymal transition
- gynecologic cancer
- gynecologic oncology
- translational science
- uterine carcinosarcoma
Fingerprint
Dive into the research topics of 'Integrated Molecular Characterization of Uterine Carcinosarcoma'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Integrated Molecular Characterization of Uterine Carcinosarcoma. / 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.; Akbani, Rehan; Ally, Adrian; Auman, J. Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B.; Beroukhim, Rameen; Bodenheimer, Tom; Bogomolniy, Faina; Boice, Lori; Bootwalla, Moiz S.; Bowen, Jay; Broaddus, Russell; Brooks, Denise; Carlsen, Rebecca; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cibulskis, Kristian; Cline, Melissa; Dao, Fanny; David, Mutch; Demchok, John A.; Dhalla, Noreen; Dowdy, Sean; Felau, Ina; Ferguson, Martin L.; Frazer, Scott; Frick, Jessica; Gabriel, Stacey; Gastier-Foster, Julie M.; Gehlenborg, Nils; Gerken, Mark; Getz, Gad; Gupta, Manaswi; Haussler, David; Hayes, D. Neil; Heiman, David I.; Hess, Julian; Hoadley, Katherine A.; Hoffmann, Robert; Holt, Robert A.; Hoyle, Alan P.; Huang, Mei; Hutter, Carolyn M.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kanchi, Rupa S.; Kandoth, Cyriac; Kasaian, Katayoon; Kerr, Sarah; Kim, Jaegil; Lai, Phillip H.; Lander, Eric; Lawrence, Michael S.; Lee, Darlene; Leraas, Kristen M.; Leshchiner, Ignaty; Levine, Douglas A.; Lichtenberg, Tara M.; Lin, Pei; Liu, Jia; Liu, Wenbin; Liu, Yuexin; Lolla, Laxmi; Lu, Yiling; Ma, Yussanne; Maglinte, Dennis T.; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Mose, Lisle E.; Mungall, Andrew J.; Mungall, Karen; Naresh, Rashi; Noble, Michael S.; Olvera, Narciso; Parker, Joel S.; Perou, Charles M.; Perou, Amy H.; Pihl, Todd; Radenbaugh, Amie J.; Ramirez, Nilsa C.; Rathmell, W. Kimryn; Roach, Jeffrey; Robertson, A. Gordon; Sadeghi, Sara; Saksena, Gordon; Salvesen, Helga B.; Schein, Jacqueline E.; Schumacher, Steven E.; Sheth, Margi; Shi, Yan; Shih, Juliann; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Sofia, Heidi J.; Soloway, Matthew G.; Sougnez, Carrie; Sun, Charlie; Tam, Angela; Tan, Donghui; Tarnuzzer, Roy; Thiessen, Nina; Thorne, Leigh B.; Tse, Kane; Tseng, Jill; Van Den Berg, David J.; Veluvolu, Umadevi; Verhaak, Roel G.W.; Voet, Doug; von Bismarck, Amanda; Wan, Yunhu; Wang, Zhining; Wang, Chen; Weinstein, John N.; Weisenberger, Daniel J.; Wilkerson, Matthew D.; Winterhoff, Boris; Wise, Lisa; Wong, Tina; Wu, Ye; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Zhang, Hailei; Zhang, Wei; Zhu, Jing chun; Zmuda, Erik; Zhang, Jiashan.
In: Cancer Cell, Vol. 31, No. 3, 13.03.2017, p. 411-423.Research output: Contribution to journal › Article › peer-review
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 - Broaddus, Russell
AU - Brooks, Denise
AU - Carlsen, Rebecca
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 - 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 - 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 - 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 - Moore, Richard A.
AU - Mose, Lisle E.
AU - Mungall, Andrew J.
AU - Mungall, Karen
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 - 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 - Sougnez, Carrie
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 - 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 - Zhang, Jiashan
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
U2 - 10.1016/j.ccell.2017.02.010
DO - 10.1016/j.ccell.2017.02.010
M3 - Article
C2 - 28292439
AN - SCOPUS:85015101723
VL - 31
SP - 411
EP - 423
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 3
ER -