Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas

Journal of Clinical Endocrinology and Metabolism

Volumn 93, Issue 10, 2008, Pages 4119-4125

  Gejman, Roger ^a   Batista, Dalia L ^a   Zhong, Ying ^a   Zhou, Yunli ^a   Zhang, Xun ^a   Swearingen, Brooke ^a   Stratakis, Constantine A ^b   Hedley Whyte, E Tessa ^a   Klibanski, Anne ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BISULFITE; GENOMIC DNA; MEG3 PROTEIN; MESSENGER RNA; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ACTH SECRETING ADENOMA; ADOLESCENT; ADULT; AGED; ARTICLE; CELL TYPE; CONTROLLED STUDY; CPG ISLAND; DNA HYPERMETHYLATION; DNA METHYLATION; FEMALE; GENE EXPRESSION; GENE LOCUS; GENE LOSS; GENE SILENCING; GROWTH HORMONE SECRETING ADENOMA; HUMAN; HUMAN TISSUE; HYPOPHYSIS ADENOMA; IMMUNOFLUORESCENCE TEST; IN SITU HYBRIDIZATION; MALE; NORTHERN BLOTTING; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL; PROLACTINOMA; REAL TIME POLYMERASE CHAIN REACTION; SCHOOL CHILD; SEQUENCE ANALYSIS;

ADENOMA; ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; CHILD; DNA METHYLATION; DNA, INTERGENIC; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE SILENCING; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; MEMBRANE PROTEINS; MIDDLE AGED; PITUITARY GLAND; PITUITARY NEOPLASMS; PROTEINS; QUANTITATIVE TRAIT LOCI; TISSUE DISTRIBUTION;

EID: 53749086981     PISSN: 0021972X     EISSN: 0021972X     Source Type: Journal    
DOI: 10.1210/jc.2007-2633     Document Type: Article

References (33)

1. Al-Shraim M, Asa SL 2006 The 2004 World Health Organization classification of pituitary tumors: what is new? Acta Neuropathol 111:1-7
2. Ezzat S, Asa SL 2006 Mechanisms of disease: the pathogenesis of pituitary tumors. Nat Clin Pract Endocrinol Metab 2:220-230
3. Grossman AB, Korbonits M 2004 Akting and cycling: a tale of the pituitary. Horm Res 62(Suppl 3):117-123
4. Alexander JM, Biller BM, Bikkal H, Zervas NT, Arnold A, Klibanski A 1990 Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest 86:336-340
5. Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S 1990 Clonal origin of pituitary adenomas. J Clin Endocrinol Metab 71:1427-1433
6. Farrell WE 2006 Pituitary tumours: findings from whole genome analyses. Endocr Relat Cancer 13:707-716
7. Melmed S 2003 Mechanisms for pituitary tumorigenesis: the plastic pituitary. J Clin Invest 112:1603-1618
8. Simpson DJ, Bicknell JE, McNicol AM, Clayton RN, Farrell WE 1999 Hypermethylation of the p16/CDKN2A/MTSI gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas. Genes Chromosomes Cancer 24:328-336
9. Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F 2000 Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells 5:211-220
10. Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A 2003 A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab 88:5119-5126
11. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A 2007 Activation of p53 by MEG3 non-coding RNA. J Biol Chem 282:24731-24742
12. Schuster-Gossler K, Bilinski P, Sado T, Ferguson-Smith A, Gossler A 1998 The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA. Dev Dyn 212:214-228
13. Croteau S, Charron MC, Latham KE, Naumova AK 2003 Alternative splicing and imprinting control of the Meg3/Gtl2-Dlk1 locus in mouse embryos. Mamm Genome 14:231-241
14. Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A 2005 Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab 90:2179-2186
15. Astuti D, Latif F, Wagner K, Gentle D, Cooper WN, Catchpoole D, Grundy R, Ferguson-Smith AC, Maher ER 2005 Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour. Br J Cancer 92:1574-1580
16. Cryns VL, Alexander JM, Klibanski A, Arnold A 1993 The retinoblastoma gene in human pituitary tumors. J Clin Endocrinol Metab 77:644-646
17. Woloschak M, Roberts JL, Post KD 1994 Loss of heterozygosity at the retinoblastoma locus in human pituitary tumors. Cancer 74:693-696
18. Woloschak M, Yu A, Post KD 1997 Frequent inactivation of the p16 gene in human pituitary tumors by gene methylation. Mol Carcinog 19:221-224
19. Woloschak M, Yu A, Xiao J, Post KD 1996 Frequent loss of the P16INK4a gene product in human pituitary tumors. Cancer Res 56:2493-2496
20. Kumar TR, Graham KE, Asa SL, Low MJ 1998 Simian virus 40 T antigen-induced gonadotroph adenomas: a model of human null cell adenomas. Endocrinology 139:3342-3351
21. Zhao J, Zhang X, Zhou Y, Ansell PJ, Klibanski A 2006 Cyclic AMP stimulates MEG3 gene expression in cells through a cAMP-response element (CRE) in the MEG3 proximal promoter region. Int J Biochem Cell Biol 38:1808-1820
22. De Cesare D, Sassone-Corsi P 2000 Transcriptional regulation by cyclic AMP-responsive factors. Prog Nucleic Acids Res Mol Biol 64:343-369
23. Richards JS 2001 New signaling pathways for hormones and cyclic adenosine 3′,5′-monophosphate action in endocrine cells. Mol Endocrinol 15:209-218
24. Paulsen M, Takada S, Youngson NA, Benchaib M, Charlier C, Segers K, Georges M, Ferguson-Smith AC 2001 Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region. Genome Res 11:2085-2094
25. Takada S, Paulsen M, Tevendale M, Tsai CE, Kelsey G, Cattanach BM, Ferguson-Smith AC 2002 Epigenetic analysis of the Dlk1-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19. Hum Mol Genet 11:77-86
26. Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaille J 2004 A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res 14:1741-1748
27. Lin SP, Youngson N, Takada S, Seitz H, Reik W, Paulsen M, Cavaille J, Ferguson-Smith AC 2003 Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12. Nat Genet 35:97-102
28. Bahar A, Bicknell JE, Simpson DJ, Clayton RN, Farrell WE 2004 Loss of expression of the growth inhibitory gene GADD45γ, in human pituitary adenomas, is associated with CpG island methylation. Oncogene 23:936-944
29. Farrell WE, Clayton RN 2003 Epigenetic change in pituitary tumorigenesis. Endocr Relat Cancer 10:323-330
30. Demura M, Bulun SE 2008 CpG dinucleotide methylation of the CYP19 I.3/II promoter modulates cAMP-stimulated aromatase activity. Mol Cell Endocrinol 283:127-132
31. Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ 2004 Epigenetic programming by maternal behavior. Nat Neurosci 7:847-854
32. Weaver IC, Champagne FA, Brown SE, Dymov S, Sharma S, Meaney MJ, Szyf M 2005 Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J Neurosci 25:11045-11054
33. Gao ZH, Suppola S, Liu J, Heikkila P, Janne J, Voutilainen R 2002 Association of H19 promoter methylation with the expression of H19 and IGF-II genes in adrenocortical tumors. J Clin Endocrinol Metab 87:1170-1176