Open AccessJournal Article
Loss of Heterozygosity on 10q23.3 and Mutation of the Tumor Suppressor Gene PTEN in Benign Endometrial Cyst of the Ovary: Possible Sequence Progression from Benign Endometrial Cyst to Endometrioid Carcinoma and Clear Cell Carcinoma of the Ovary
Nakako Sato,Hajime Tsunoda,Masato Nishida,Yukio Morishita,Yasuhiko Takimoto,Takeshi Kubo,Masayuki Noguchi +6 more
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TLDR
Results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.Abstract:
Loss of heterozygosity (LOH) at locus 10q23.3 and mutation of the PTEN tumor suppressor gene occur frequently in both endometrial carcinoma and ovarian endometrioid carcinoma. To investigate the potential role of the PTEN gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%), and 13 of 23 solitary endometrial cysts (56.5%). In 5 endometrioid carcinomas synchronous with endometriosis, 3 cases displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 1 displayed no LOH events in either lesion. In 7 clear cell carcinomas synchronous with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 3 displayed no LOH events in either lesion. In no cases were there LOH events in the endometriosis only. Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%). These results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.read more
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Journal ArticleDOI
ARID1A mutations in endometriosis-associated ovarian carcinomas.
Kimberly C. Wiegand,Sohrab P. Shah,Osama M. Al-Agha,Yongjun Zhao,Kane Tse,Thomas Zeng,Janine Senz,Melissa K. McConechy,Michael S. Anglesio,Steve E. Kalloger,Winnie Yang,Alireza Heravi-Moussavi,Ryan Giuliany,Christine Chow,John Fee,Abdalnasser Zayed,Leah M Prentice,Nataliya Melnyk,Gulisa Turashvili,Allen Delaney,Jason Madore,Stephen Yip,Andrew McPherson,Gavin Ha,Lynda Bell,Sian Fereday,Angela Tam,Laura Galletta,Patricia N. Tonin,Diane Provencher,Dianne Miller,Steven J.M. Jones,Richard A. Moore,Gregg B. Morin,Gregg B. Morin,Arusha Oloumi,Niki Boyd,Samuel Aparicio,Ie Ming Shih,Anne Marie Mes-Masson,David D.L. Bowtell,David D.L. Bowtell,Martin Hirst,Blake Gilks,Marco A. Marra,Marco A. Marra,David G. Huntsman +46 more
TL;DR: These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas.
Journal ArticleDOI
Ovarian Tumorigenesis : A Proposed Model Based on Morphological and Molecular Genetic Analysis
Ie Ming Shih,Robert J. Kurman +1 more
TL;DR: This model of carcinogenesis reconciles the relationship of borderline tumors to invasive carcinoma and provides a morphological and molecular framework for studies aimed at elucidating the pathogenesis of ovarian cancer.
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Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma
Siân Jones,Tian Li Wang,Ie Ming Shih,Tsui Lien Mao,Kentaro Nakayama,Richard B.S. Roden,Ruth Glas,Dennis J. Slamon,Luis A. Diaz,Bert Vogelstein,Kenneth W. Kinzler,Victor E. Velculescu,Nickolas Papadopoulos +12 more
TL;DR: The nature and pattern of the mutations suggest that PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor gene contributes to the pathogenesis of OCCC.
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Pathogenesis and pathophysiology of endometriosis
TL;DR: The disease process is reviewed from theories regarding origin to the molecular basis for disease sequelae and a thorough understanding of the histopathogenesis and pathophysiology of endometriosis is essential to the development of novel diagnostic and treatment approaches for this debilitating condition.
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Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—Shifting the paradigm
Robert J. Kurman,Ie Ming Shih +1 more
TL;DR: It now appears that type I and type II ovarian tumors develop independently along different molecular pathways and that both types develop outside the ovary and involve it secondarily, leading to the conclusion that the only true primary ovarian neoplasms are gonadal stromal and germ cell tumors analogous to testicular tumors.
References
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Journal ArticleDOI
PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Jing Li,Clifford Yen,Danny Liaw,Katrina Podsypanina,Shikha Bose,Steven I. Wang,Janusz Puc,Christa Miliaresis,Linda Rodgers,Richard W. McCombie,Sandra H. Bigner,Beppino C. Giovanella,Michael Ittmann,B. Tycko,Hanina Hibshoosh,Michael Wigler,Ramon Parsons +16 more
TL;DR: The PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions as discussed by the authors.
Journal ArticleDOI
The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate
Tomohiko Maehama,Jack E. Dixon +1 more
TL;DR: It is demonstrated that overexpression of PTEN, a putative tumor suppressor, reduced insulin-induced PtdIns(3,4,5)P3 production in human 293 cells without effecting insulin- induced phosphoinositide 3-kinase activation.
Journal ArticleDOI
Identification of a candidate tumour suppressor gene, MMAC1 , at chromosome 10q23.3 that is mutated in multiple advanced cancers
Peter A. Steck,Mark A. Pershouse,Samar A. Jasser,W. K. A. Yung,Huai Lin,Azra H. Ligon,Lauren A. Langford,Michelle Baumgard,T. Hattier,Thaylon Davis,Cheryl Frye,Rong Hu,Bradley D. Swedlund,David H. F. Teng,Sean V. Tavtigian +14 more
TL;DR: The results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.
Journal ArticleDOI
Laser Capture Microdissection
Michael R. Emmert-Buck,Robert F. Bonner,Paul D. Smith,Rodrigo F. Chuaqui,Zhengping Zhuang,Seth R. Goldstein,Rhonda A. Weiss,Lance A. Liotta +7 more
TL;DR: Laser capture microdissection under direct microscopic visualization permits rapid one-step procurement of selected human cell populations from a section of complex, heterogeneous tissue.
Journal ArticleDOI
Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome
Danny Liaw,Deborah J. Marsh,Jing Li,Patricia L. M. Dahia,Steven I. Wang,Z. Zheng,Shikha Bose,K. M. Call,Hui C. Tsou,Monica Peacocke,Charis Eng,Ramon Parsons +11 more
TL;DR: Mutational analysis of PTEN in CD kindreds has identified germline mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene, and implies that PTEN may play a role in organizing the relationship of different cell types within an organ during development.
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ARID1A mutations in endometriosis-associated ovarian carcinomas.
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