Roles of Deletion of Arid1a, a Tumor Suppressor, in Mouse Ovarian Tumorigenesis

被引：106

作者：

Guan, Bin ^{[1
,2
]}

Rahmanto, Yohan Suryo ^{[1
,2
]}

Wu, Ren-Chin ^{[1
,2
,3
,4
]}

Wang, Yihong ^{[1
,2
]}

Wang, Zhong ^{[5
]}

Wang, Tian-Li ^{[1
,2
]}

Shih, Ie-Ming ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Dept Gynecol & Obstet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[3] Chang Gung Mem Hosp, Dept Pathol, Taoyuan, Taiwan

[4] Chang Gung Univ, Coll Med, Taoyuan, Taiwan

[5] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2014年 / 106卷 / 07期

基金：

美国国家卫生研究院;

关键词：

GRADE ENDOMETRIOID CARCINOMA; REMODELING GENE ARID1A; UNDIFFERENTIATED CARCINOMA; CLEAR-CELL; PTEN; EXPRESSION; MUTATIONS; CANCER; ADENOCARCINOMA; PROGRESSION;

D O I：

10.1093/jnci/dju146

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The chromatin remodeling gene, ARID1A, has been implied as a tumor suppressor, and its somatic inactivating mutations occur in a wide variety of human cancers, most frequently in ovarian and uterine endometrioid and ovarian clear cell carcinomas. Tumors with ARID1A mutations also frequently harbor PTEN or PIK3CA mutations, suggesting their collaboration in tumorigenesis. Here, we used a conditional knockout mouse model in which Arid1a and Pten were deleted either individually or in combination in the mouse ovarian surface epithelium. After 6 months, 59.1% of mice with Arid1a and Pten double knockout developed ovarian endometrioid or undifferentiated carcinoma, whereas the remaining mice showed hyperplasia of ovarian surface epithelium. In contrast, 52 mice with homozygous or heterozygous deletion in either Arid1a or Pten did not develop ovarian lesions. These results demonstrate that inactivation of Arid1a alone is insufficient for tumor initiation but it requires additional genetic alteration(s) such as Pten deletion to drive tumorigenesis.

引用

页数：4

共 27 条

[1]

Undifferentiated carcinoma of the endometrium [J].

Altrabulsi, B ;

Malpica, A ;

Deavers, MT ;

Bodurka, DC ;

Broaddus, R ;

Silva, EG .

AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2005, 29 (10) :1316-1321

[2]

Loss of ARID1A Expression Is an Early Molecular Event in Tumor Progression From Ovarian Endometriotic Cyst to Clear Cell and Endometrioid Carcinoma [J].

Ayhan, Ayse ;

Mao, Tsui-Lien ;

Seckin, Tamer ;

Wu, Chen-Hsuan ;

Guan, Bin ;

Ogawa, Hiroshi ;

Futagami, Masayuki ;

Mizukami, Hiroki ;

Yokoyama, Yoshihito ;

Kurman, Robert J. ;

Shih, Ie-Ming .

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2012, 22 (08) :1310-1315

[3]

PTEN, more than the AKT pathway [J].

Blanco-Aparicio, Carmen ;

Renner, Oliver ;

Leal, Juan F. M. ;

Carnero, Amancio .

CARCINOGENESIS, 2007, 28 (07) :1379-1386

[4]

Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers [J].

Chan-on, Waraporn ;

Nairismaegi, Maarja-Liisa ;

Ong, Choon Kiat ;

Lim, Weng Khong ;

Dima, Simona ;

Pairojkul, Chawalit ;

Lim, Kiat Hon ;

McPherson, John R. ;

Cutcutache, Ioana ;

Heng, Hong Lee ;

Ooi, London ;

Chung, Alexander ;

Chow, Pierce ;

Cheow, Peng Chung ;

Lee, Ser Yee ;

Choo, Su Pin ;

Tan, Iain Bee Huat ;

Duda, Dan ;

Nastase, Anca ;

Myint, Swe Swe ;

Wong, Bernice Huimin ;

Gan, Anna ;

Rajasegaran, Vikneswari ;

Ng, Cedric Chuan Young ;

Nagarajan, Sanjanaa ;

Jusakul, Apinya ;

Zhang, Shenli ;

Vohra, Priya ;

Yu, Willie ;

Huang, DaChuan ;

Sithithaworn, Paiboon ;

Yongvanit, Puangrat ;

Wongkham, Sopit ;

Khuntikeo, Narong ;

Bhudhisawasdi, Vajaraphongsa ;

Popescu, Irinel ;

Rozen, Steven G. ;

Tan, Patrick ;

Teh, Bin Tean .

NATURE GENETICS, 2013, 45 (12) :1474-U100

[5]

Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer [J].

Dinulescu D.M. ;

Ince T.A. ;

Quade B.J. ;

Shafer S.A. ;

Crowley D. ;

Jacks T. .

Nature Medicine, 2005, 11 (1) :63-70

[6]

Flesken-Nikitin A, 2003, CANCER RES, V63, P3459

[7]

Integrated genomic characterization of endometrial carcinoma [J].

Getz, Gad ;

Gabriel, Stacey B. ;

Cibulskis, Kristian ;

Lander, Eric ;

Sivachenko, Andrey ;

Sougnez, Carrie ;

Lawrence, Mike ;

Kandoth, Cyriac ;

Dooling, David ;

Fulton, Robert ;

Fulton, Lucinda ;

Kalicki-Veizer, Joelle ;

McLellan, Michael D. ;

O'Laughlin, Michelle ;

Schmidt, Heather ;

Wilson, Richard K. ;

Ye, Kai ;

Ding, Li ;

Mardis, Elaine R. ;

Ally, Adrian ;

Balasundaram, Miruna ;

Birol, Inanc ;

Butterfield, Yaron S. N. ;

Carlsen, Rebecca ;

Carter, Candace ;

Chu, Andy ;

Chuah, Eric ;

Chun, Hye-Jung E. ;

Dhalla, Noreen ;

Guin, Ranabir ;

Hirst, Carrie ;

Holt, Robert A. ;

Jones, Steven J. M. ;

Lee, Darlene ;

Li, Haiyan I. ;

Marra, Marco A. ;

Mayo, Michael ;

Moore, Richard A. ;

Mungall, Andrew J. ;

Plettner, Patrick ;

Schein, Jacqueline E. ;

Sipahimalani, Payal ;

Tam, Angela ;

Varhol, Richard J. ;

Robertson, A. Gordon ;

Pashtan, Itai ;

Saksena, Gordon ;

Onofrio, Robert C. ;

Schumacher, Steven E. ;

Tabak, Barbara .

NATURE, 2013, 497 (7447) :67-73

[8]

Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo [J].

Groszer, M ;

Erickson, R ;

Scripture-Adams, DD ;

Lesche, R ;

Trumpp, A ;

Zack, JA ;

Kornblum, HI ;

Liu, X ;

Wu, H .

SCIENCE, 2001, 294 (5549) :2186-2189

[9]

ARID1A, a Factor That Promotes Formation of SWI/SNF-Mediated Chromatin Remodeling, Is a Tumor Suppressor in Gynecologic Cancers [J].

Guan, Bin ;

Wang, Tian-Li ;

Shih, Ie-Ming .

CANCER RESEARCH, 2011, 71 (21) :6718-6727

[10]

Mutation and Loss of Expression of ARID1A in Uterine Low-grade Endometrioid Carcinoma [J].

Guan, Bin ;

Mao, Tsui-Lien ;

Panuganti, Pradeep K. ;

Kuhn, Elisabetta ;

Kurman, Robert J. ;

Maeda, Daichi ;

Chen, Elizabeth ;

Jeng, Yung-Ming ;

Wang, Tian-Li ;

Shih, Ie-Ming .

AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2011, 35 (05) :625-632

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