Integrated Molecular Characterization of Uterine Carcinosarcoma

被引：372

作者：

Cherniack, Andrew D. ^{[1
,2
]}

Shen, Hui ^{[3
]}

Walter, Vonn ^{[4
]}

Stewart, Chip ^{[1
,2
]}

Murray, Bradley A. ^{[1
,2
]}

Bowlby, Reanne ^{[5
]}

Hu, Xin ^{[6
]}

Ling, Shiyun ^{[6
]}

Soslow, Robert A. ^{[7
]}

Broaddus, Russell R. ^{[6
]}

Zuna, Rosemary E. ^{[8
]}

Robertson, Gordon ^{[5
]}

Laird, Peter W. ^{[3
]}

Kucherlapati, Raju ^{[9
]}

Mills, Gordon B. ^{[6
]}

Weinstein, John N. ^{[6
]}

Zhang, Jiashan ^{[10
]}

Akbani, Rehan ^{[6
]}

Levine, Douglas A. ^{[11
]}

机构：

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

[2] Harvard Univ, Cambridge, MA 02142 USA

[3] Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA

[4] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

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

[6] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[7] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

[8] Univ Oklahoma, Hlth Sci Ctr, Stephenson Canc Ctr, Oklahoma City, OK 73104 USA

[9] Harvard Med Sch, Boston, MA 02115 USA

[10] NCI, Bethesda, MD 20892 USA

[11] NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, 550 1St Ave, New York, NY 10016 USA

来源：

CANCER CELL | 2017年 / 31卷 / 03期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; MIXED MULLERIAN TUMORS; COPY-NUMBER ALTERATION; ENDOMETRIAL CARCINOMAS; SENSITIZES CELLS; CANCER; HETEROGENEITY; ARID1A; GENES; RESISTANCE;

D O I：

10.1016/j.ccell.2017.02.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：411 / 423

页数：13

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