To characterize and define the role of MEG3, a pituitary derived gene, to increase the understating of its role in human pituitary tumors which represent up to 40% of all diagnosed pituitary neoplasms. These tumors commonly lead to visual loss and many other severe neurologic and endocrine deficits.

Public Health Relevance

Human pituitary tumors of a gonadotroph cell origin represent up to 40% of all diagnosed pituitary neoplasms, can cause visual loss and other neurologic deficits, and have no established medical treatment. We have found a pituitary-derived gene, MEG3, which may function as a tumor suppressor. Investigation of the function of this gene will provide important information regarding the pathogenesis of human pituitary adenomas, and, potentially, other human tumors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040947-16
Application #
7849747
Study Section
Molecular and Cellular Endocrinology Study Section (MCE)
Program Officer
Malozowski, Saul N
Project Start
1989-03-01
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2012-07-31
Support Year
16
Fiscal Year
2010
Total Cost
$381,427
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Zhou, Yunli; Zhang, Xun; Klibanski, Anne (2014) Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma. Mol Cell Endocrinol 386:16-33
Zhou, Yunli; Zhang, Xun; Klibanski, Anne (2012) MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol 48:R45-53
Cheunsuchon, Pornsuk; Zhou, Yunli; Zhang, Xun et al. (2011) Silencing of the imprinted DLK1-MEG3 locus in human clinically nonfunctioning pituitary adenomas. Am J Pathol 179:2120-30
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Zhang, Xun; Rice, Kimberley; Wang, Yingying et al. (2010) Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions. Endocrinology 151:939-47
Zhang, Xun; Zhou, Yunli; Klibanski, Anne (2010) Isolation and characterization of novel pituitary tumor related genes: a cDNA representational difference approach. Mol Cell Endocrinol 326:40-7
Zhou, Yunli; Cheunsuchon, Pornsuk; Nakayama, Yuki et al. (2010) Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene. Development 137:2643-52
Gejman, Roger; Batista, Dalia L; Zhong, Ying et al. (2008) Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 93:4119-25

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