Epigenetic regulation of mucin genes in human cancers

Clinical Epigenetics

Volumn 2, Issue 2, 2011, Pages 85-96

  Yamada, Norishige ^a   Kitamoto, Sho ^a   Yokoyama, Seiya ^a   Hamada, Tomofumi ^a   Goto, Masamichi ^a,b   Tsutsumida, Hideaki ^a   Higashi, Michiyo ^a   Yonezawa, Suguru ^a  

^a KAGOSHIMA UNIVERSITY   (Japan)

^b National Sanatorium Hoshizuka Keiaien   (Japan)

Author keywords

Cancer; DNA methylation; Epigenetics; Histone modification; Micro RNAs; Mucin

Indexed keywords

HISTONE H3; MUCIN; MUCIN 1; MUCIN 16; MUCIN 17; MUCIN 2; MUCIN 3; MUCIN 3A; MUCIN 4; MUCIN 5AC; MUCIN 5B; MUCIN 6; UNCLASSIFIED DRUG;

5' UNTRANSLATED REGION; BREAST CANCER; CANCER GENETICS; CANCER PROGNOSIS; CHROMATIN IMMUNOPRECIPITATION; COLON CANCER; CPG ISLAND; DNA DETERMINATION; DNA METHYLATION; DOWN REGULATION; EPIGENETICS; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE IDENTIFICATION; GENE LOCATION; GENE OVEREXPRESSION; GENETIC ASSOCIATION; GENETIC RISK; HISTONE MODIFICATION; HUMAN; MOLECULAR PATHOLOGY; MUCIN 1 GENE; MUCIN 16 GENE; MUCIN 17 GENE; MUCIN 2 GENE; MUCIN 3A GENE; MUCIN 4 GENE; MUCIN 5AC GENE; MUCIN 5B GENE; MUCIN 6 GENE; MUCIN GENE; NONHUMAN; ONCOGENE; PANCREAS CANCER; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROMOTER REGION; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PYROSEQUENCING; REGULATOR GENE; REVIEW; TRANSCRIPTION INITIATION SITE; UPREGULATION;

EID: 82455191552     PISSN: 18687075     EISSN: 18687083     Source Type: Journal    
DOI: 10.1007/s13148-011-0037-3     Document Type: Review

References (133)

1. Alvarez-Venegas R, Avramova Z (2005) Methylation patterns of histone H3 Lys 4, Lys 9 and Lys 27 in transcriptionally active and inactive Arabidopsis genes and in atx1 mutants. Nucleic Acids Res 33:5199-5207 (Pubitemid 41508680)
2. Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H, Hollingsworth MA et al (2001) Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res 7:4033-4040 (Pubitemid 34044624)
3. Audie JP, Janin A, Porchet N, Copin MC, Gosselin B, Aubert JP (1993) Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization. J Histochem Cytochem 41:1479-1485 (Pubitemid 23275249)
4. Audie JP, Tetaert D, Pigny P, Buisine MP, Janin A, Aubert JP et al (1995) Mucin gene expression in the human endocervix. Hum Reprod 10:98-102
5. Bartman AE, Buisine MP, Aubert JP, Niehans GA, Toribara NW, Kim YS et al (1998) The MUC6 secretory mucin gene is expressed in a wide variety of epithelial tissues. J Pathol 186:398-405 (Pubitemid 29005459)
6. Bhaskar KR, Garik P, Turner BS, Bradley JD, Bansil R, Stanley HE et al (1992) Viscous fingering of HCl through gastric mucin. Nature 360:458-461
7. Bird A (1992) The essentials of DNA methylation. Cell 70:5-8
8. Brakensiek K, Wingen LU, Langer F, Kreipe H, Lehmann U (2007) Quantitative high-resolution CpG island mapping with pyrosequencing reveals disease-specific methylation patterns of the CDKN2B gene in myelodysplastic syndrome and myeloid leukemia. Clin Chem 53:17-23 (Pubitemid 46047759)
9. Buisine MP, Devisme L, Copin MC, Durand-Reville M, Gosselin B, Aubert JP et al (1999) Developmental mucin gene expression in the human respiratory tract. Am J Respir Cell Mol Biol 20:209-218 (Pubitemid 129504880)
10. Chang SK, Dohrman AF, Basbaum CB, Ho SB, Tsuda T, Toribara NW et al (1994) Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer. Gastroenterology 107:28-36 (Pubitemid 24195342)
11. Chen Y, Zhao YH, Kalaslavadi TB, Hamati E, Nehrke K, Le AD et al (2004) Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissues. Am J Respir Cell Mol Biol 30:155-165 (Pubitemid 38147200)
12. Crawley SC, Gum JR Jr, Hicks JW, PrattWS, Aubert JP, Swallow DMet al (1999) Genomic organization and structure of the 3′ region of human MUC3: alternative splicing predicts membrane-bound and soluble forms of the mucin. Biochem Biophys Res Commun 263:728-736 (Pubitemid 29490695)
13. Das PM, Singal R (2004) DNA methylation and cancer. J Clin Oncol 22:4632-4642 (Pubitemid 41185132)
14. DeAngelis JT, Farrington WJ, Tollefsbol TO (2008) An overview of epigenetic assays. Mol Biotechnol 38:179-183
15. Desseyn JL, Guyonnet-Duperat V, Porchet N, Aubert JP, Laine A (1997) Human mucin gene MUC5B, the 10.7-kb large central exon encodes various alternate subdomains resulting in a superrepeat. Structural evidence for a 11p15.5 gene family. J Biol Chem 272:3168-3178
16. Desseyn JL, Buisine MP, Porchet N, Aubert JP, Degand P, Laine A (1998) Evolutionary history of the 11p15 human mucin gene family. J Mol Evol 46:102-106 (Pubitemid 28047243)
17. Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G et al (2005) Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci USA 102:15785-15790 (Pubitemid 41552820)
18. Fullwood MJ, Ruan Y (2009) ChIP-based methods for the identification of long-range chromatin interactions. J Cell Biochem 107:30-39
19. Garinis GA, Patrinos GP, Spanakis NE, Menounos PG (2002) DNA hypermethylation: when tumour suppressor genes go silent. Hum Genet 111:115-127 (Pubitemid 36075029)
20. Gipson IK, Spurr-Michaud S, Moccia R, Zhan Q, Toribara N, Ho SB et al (1999) MUC4 and MUC5B transcripts are the prevalent mucin messenger ribonucleic acids of the human endocervix. Biol Reprod 60:58-64 (Pubitemid 29022350)
21. Gratchev A, Siedow A, Bumke-Vogt C, Hummel M, Foss HD, Hanski ML et al (2001) Regulation of the intestinal mucin MUC2 gene expression in vivo: evidence for the role of promoter methylation. Cancer Lett 168:71-80 (Pubitemid 32463915)
22. Gum JR, Hicks JW, Swallow DM, Lagace RL, Byrd JC, Lamport DT et al (1990) Molecular cloning of cDNAs derived from a novel human intestinal mucin gene. Biochem Biophys Res Commun 171:407-415 (Pubitemid 20283222)
23. Gum JR Jr, Ho JJ, Pratt WS, Hicks JW, Hill AS, Vinall LE et al (1997) MUC3 human intestinal mucin. Analysis of gene structure, the carboxyl terminus, and a novel upstream repetitive region. J Biol Chem 272:26678-26686 (Pubitemid 27458893)
24. Gum JR Jr, Crawley SC, Hicks JW, Szymkowski DE, Kim YS (2002) MUC17, a novel membrane-tethered mucin. Biochem Biophys Res Commun 291:466-475 (Pubitemid 34687369)
25. Hamada T, Goto M, Tsutsumida H, Nomoto M, Higashi M, Sugai T et al (2005) Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell lines, using bisulfite genomic sequencing. Cancer Lett 227:175-184 (Pubitemid 41169931)
26. Handra-Luca A, Lamas G, Bertrand JC, Fouret P (2005) MUC1, MUC2, MUC4, and MUC5AC expression in salivary gland mucoepidermoid carcinoma: diagnostic and prognostic implications. Am J Surg Pathol 29:881-889 (Pubitemid 40885010)
27. Hanski C, Riede E, Gratchev A, Foss HD, Bohm C, Klussmann E et al (1997) MUC2 gene suppression in human colorectal carcinomas and their metastases: in vitro evidence of the modulatory role of DNA methylation. Lab Invest 77:685-695 (Pubitemid 28018790)
28. Hartmann C, Corre-Menguy F, Boualem A, Jovanovic M, Lelandais-Briere C (2004) MicroRNAs: a new class of gene expression regulators. Med Sci (Paris) 20:894-898 (Pubitemid 39387604)
29. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522-531 (Pubitemid 38868508)
30. Higashi M, Yonezawa S, Ho JJ, Tanaka S, Irimura T, Kim YS et al (1999) Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: its relationship with a new morphological classification of cholangiocarcinoma. Hepatology 30:1347-1355
31. Higuchi T, Orita T, Katsuya K, Yamasaki Y, Akiyama K, Li H et al (2004) MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met. Mol Cell Biol 24:7456-7468 (Pubitemid 39121474)
32. Hiraki M, Kitajima Y, Sato S, Nakamura J, Hashiguchi K, Noshiro H et al (2010) Aberrant gene methylation in the peritoneal fluid is a risk factor predicting peritoneal recurrence in gastric cancer. World J Gastroenterol 16:330-338
33. Hirono S, Yamaue H, Hoshikawa Y, Ina S, Tani M, Kawai M et al (2010) Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome-wide expression profiling. Cancer Sci 101:259-266
34. Ho JJ, Han SW, Pan PL, Deng G, Kuan SF, Kim YS (2003) Methylation status of promoters and expression ofMUC2 andMUC5ACmucins in pancreatic cancer cells. Int J Oncol 22:273-279
35. Ho SB, Dvorak LA, Moor RE, Jacobson AC, Frey MR, Corredor J et al (2006) Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing. Gastroenterology 131:1501-1517 (Pubitemid 44708946)
36. Hollingsworth MA, Swanson BJ (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4:45-60 (Pubitemid 38082153)
37. Horinouchi M, Nagata K, Nakamura A, Goto M, Takao S, Sakamoto M et al (2003) Expression of different glycoforms of membrane mucin (MUC1) and secretory mucin (MUC2, MUC5AC and MUC6) in pancreatic neoplasms. Acta Histochem Cytochem 36:443-453 (Pubitemid 37433062)
38. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P et al (2009) The human colon cancer methylome shows similar hypo-and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41:178-186
39. Itoh Y, Kamata-Sakurai M, Denda-Nagai K, Nagai S, Tsuiji M, Ishii-Schrade K et al (2008) Identification and expression of human epiglycanin/MUC21: a novel transmembrane mucin. Glycobiology 18:74-83
40. Jin C, Rajabi H, Kufe D (2010) miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death. Int J Oncol 37:61-69
41. Jonckheere N, Perrais M, Mariette C, Batra SK, Aubert JP, Pigny P et al (2004) A role for human MUC4 mucin gene, the ErbB2 ligand, as a target of TGF-beta in pancreatic carcinogenesis. Oncogene 23:5729-5738 (Pubitemid 39093018)
42. Kamalakaran S, Varadan V, Giercksky Russnes HE, Levy D, Kendall J, Janevski A et al (2011) DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables. Mol Oncol 5 (1):77-92
43. Kamio K, Matsushita I, Hijikata M, Kobashi Y, Tanaka G, Nakata K et al (2005) Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis. Am J Respir Crit Care Med 171:949-957 (Pubitemid 40616942)
44. Kim GE, Bae HI, Park HU, Kuan SF, Crawley SC, Ho JJ et al (2002) Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterology 123:1052-1060
45. Kitamoto S, Yamada N, Yokoyama S, Houjou I, Higashi M, Yonezawa S (2010) Promoter hypomethylation contributes to the expression of MUC3A in cancer cells. Biochem Biophys Res Commun 397:333-339
46. Kitamoto S, Yamada N, Yokoyama S, Houjou I, Higashi M, Goto M et al (2011) DNA methylation and histone H3-K9 modifications contribute to MUC17 expression. Glycobiology 21:247-256
47. Kitamura H, Yonezawa S, Tanaka S, Kim YS, Sato E (1996) Expression of mucin carbohydrates and core proteins in carcinomas of the ampulla of Vater: their relationship to prognosis. Jpn J Cancer Res 87:631-640 (Pubitemid 26235555)
48. Kondo Y, Shen L, Issa JP (2003) Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer. Mol Cell Biol 23:206-215 (Pubitemid 36008514)
49. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597-610
50. Kufe DW (2009) Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 9:874-885
51. Lan MS, Batra SK, Qi WN, Metzgar RS, Hollingsworth MA (1990) Cloning and sequencing of a human pancreatic tumor mucin cDNA. J Biol Chem 265:15294-15299
52. Lee BB, Lee EJ, Jung EH, Chun HK, Chang DK, Song SY et al (2009) Aberrant methylation of APC, MGMT, RASSF2A, and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res 15:6185-6191
53. Lehmann JM, Riethmuller G, Johnson JP (1989) MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci USA 86:9891-9895 (Pubitemid 20030740)
54. Lenhard K, Bommer GT, Asutay S, Schauer R, Brabletz T, Goke B et al (2005) Analysis of promoter methylation in stool: a novel method for the detection of colorectal cancer. Clin Gastroenterol Hepatol 3:142-149 (Pubitemid 40220309)
55. Leroy X, Gouyer V, Ballereau C, Zerimech F, Huet G, Copin MC et al (2003) Quantitative RT-PCR assay for MUC3 and VEGF mRNA in renal clear cell carcinoma: relationship with nuclear grade and prognosis. Urology 62:771-775 (Pubitemid 37205031)
56. Liang G, Lin JC, Wei V, Yoo C, Cheng JC, Nguyen CT et al (2004) Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc Natl Acad Sci USA 101:7357-7362 (Pubitemid 38638037)
57. Linden S, Mahdavi J, Hedenbro J, Boren T, Carlstedt I (2004) Effects of pH on Helicobacter pylori binding to human gastric mucins: identification of binding to non-MUC5AC mucins. Biochem J 384:263-270 (Pubitemid 39656238)
58. Linden SK, Sutton P, Karlsson NG, Korolik V, McGuckin MA (2008) Mucins in the mucosal barrier to infection. Mucosal Immunol 1:183-197 (Pubitemid 351541304)
59. Lujambio A, Esteller M (2007) CpG island hypermethylation of tumor suppressor microRNAs in human cancer. Cell Cycle 6:1455-1459
60. Marmorstein R (2001) Protein modules that manipulate histone tails for chromatin regulation. Nat Rev Mol Cell Biol 2:422-432 (Pubitemid 33680581)
61. Matsubayashi H, Canto M, Sato N, Klein A, Abe T, Yamashita K et al (2006) DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease. Cancer Res 66:1208-1217 (Pubitemid 43165992)
62. Matsukita S, Nomoto M, Kitajima S, Tanaka S, Goto M, Irimura T et al (2003) Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinoma. Histopathology 42:26-36 (Pubitemid 36062564)
63. Medina PP, Slack FJ (2008) MicroRNAs and cancer: an overview. Cell Cycle 7:2485-2492
64. Mesquita P, Peixoto AJ, Seruca R, Hanski C, Almeida R, Silva F et al (2003) Role of site-specific promoter hypomethylation in aberrant MUC2 mucin expression in mucinous gastric carcinomas. Cancer Lett 189:129-136 (Pubitemid 35469124)
65. Moehle C, Ackermann N, Langmann T, Aslanidis C, Kel A, Kel-Margoulis O et al (2006) Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. J Mol Med 84:1055-1066
66. Moniaux N, Escande F, Porchet N, Aubert JP, Batra SK (2001) Structural organization and classification of the human mucin genes. Front Biosci 6:D1192-D1206
67. Moniaux N, Junker WM, Singh AP, Jones AM, Batra SK (2006) Characterization of human mucin MUC17. Complete coding sequence and organization. J Biol Chem 281:23676-23685 (Pubitemid 44274143)
68. Munshi A, Shafi G, Aliya N, Jyothy A (2009) Histone modifications dictate specific biological readouts. J Genet Genomics 36:75-88
69. Mutskov V, Felsenfeld G (2004) Silencing of transgene transcription precedes methylation of promoter DNA and histone H3 lysine 9. EMBO J 23:138-149 (Pubitemid 38165754)
70. Nagata K, Horinouchi M, Saitou M, Higashi M, Nomoto M, Goto M et al (2007) Mucin expression profile in pancreatic cancer and the precursor lesions. J Hepatobiliary Pancreat Surg 14:243-254 (Pubitemid 46863913)
71. Nakahara K, Carthew RW (2004) Expanding roles for miRNAs and siRNAs in cell regulation. Curr Opin Cell Biol 16:127-133 (Pubitemid 38757288)
72. Nakamura A, Horinouchi M, Goto M, Nagata K, Sakoda K, Takao S et al (2002) New classification of pancreatic intraductal papillarymucinous tumour by mucin expression: its relationship with potential for malignancy. J Pathol 197:201-210 (Pubitemid 34567608)
73. Nguyen CT, Weisenberger DJ, Velicescu M, Gonzales FA, Lin JC, Liang G et al (2002) Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′- deoxycytidine. Cancer Res 62:6456-6461 (Pubitemid 35364106)
74. O'Brien TJ, Beard JB, Underwood LJ, Dennis RA, Santin AD, York L (2001) The CA 125 gene: an extracellular superstructure dominated by repeat sequences. Tumour Biol 22:348-366 (Pubitemid 34062947)
75. O'Brien TJ, Beard JB, Underwood LJ, Shigemasa K (2002) The CA 125 gene: a newly discovered extension of the glycosylated Nterminal domain doubles the size of this extracellular superstructure. Tumour Biol 23:154-169 (Pubitemid 44858307)
76. Oka M, Meacham AM, Hamazaki T, Rodic N, Chang LJ, Terada N (2005) De novo DNA methyltransferases Dnmt3a and Dnmt3b primarily mediate the cytotoxic effect of 5-aza-2′-deoxycytidine. Oncogene 24:3091-3099 (Pubitemid 40695078)
77. Okudaira K, Kakar S, Cun L, Choi E, Wu Decamillis R, Miura S et al (2010) MUC2 gene promoter methylation in mucinous and nonmucinous colorectal cancer tissues. Int J Oncol 36:765-775
78. Osako M, Yonezawa S, Siddiki B, Huang J, Ho JJ, Kim YS et al (1993) Immunohistochemical study of mucin carbohydrates and core proteins in human pancreatic tumors. Cancer 71:2191-2199 (Pubitemid 23087755)
79. Park HU, Kim JW, Kim GE, Bae HI, Crawley SC, Yang SC et al (2003) Aberrant expression of MUC3 and MUC4 membraneassociated mucins and sialyl Le(x) antigen in pancreatic intraepithelial neoplasia. Pancreas 26:e48-e54
80. Patton S, Gendler SJ, Spicer AP (1995) The epithelial mucin, MUC1, of milk, mammary gland and other tissues. Biochim Biophys Acta 1241:407-423 (Pubitemid 26021828)
81. Peng DF, Kanai Y, Sawada M, Ushijima S, Hiraoka N, Kosuge T et al (2005) Increased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas. Cancer Sci 96:403-408 (Pubitemid 41179741)
82. Perrais M, Pigny P, Buisine MP, Porchet N, Aubert JP, Van Seuningen-Lempire I (2001) Aberrant expression of human mucin gene MUC5B in gastric carcinoma and cancer cells. Identification and regulation of a distal promoter. J Biol Chem 276:15386-15396
83. Pinto-de-Sousa J, Reis CA, David L, Pimenta A, Cardoso-de-Oliveira M (2004) MUC5B expression in gastric carcinoma: relationship with clinico-pathological parameters and with expression of mucins MUC1, MUC2, MUC5AC and MUC6. Virchows Arch 444:224-230 (Pubitemid 38446433)
84. Rajabi H, Jin C, Ahmad R, McClary C, Joshi MD, Kufe D (2010) Mucin 1 oncoprotein expression is suppressed by the miR-125b Oncomir. Genes Cancer 1:62-68
85. Rakha EA, Boyce RW, Abd El-Rehim D, Kurien T, Green AR, Paish EC et al (2005) Expression of mucins (MUC1, MUC2, MUC3 MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol 18:1295-1304 (Pubitemid 41348648)
86. Rodriguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17:330-339
87. Ronaghi M (2001) Pyrosequencing sheds light on DNA sequencing. Genome Res 11:3-11 (Pubitemid 32117949)
88. Sachdeva M, Mo YY (2010) MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res 70:378-387
89. Sagara M, Yonezawa S, Nagata K, Tezuka Y, Natsugoe S, Xing PX et al (1999) Expression of mucin 1 (MUC1) in esophageal squamous-cell carcinoma: its relationship with prognosis. Int J Cancer 84:251-257 (Pubitemid 29256750)
90. Saito Y, Jones PA (2006) Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle 5:2220-2222 (Pubitemid 44546557)
91. Saitou M, Goto M, Horinouchi M, Tamada S, Nagata K, Hamada T et al (2005) MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas. J Clin Pathol 58:845-852 (Pubitemid 41113392)
92. Sato N, Maitra A, Fukushima N, van Heek NT, Matsubayashi H, Iacobuzio-Donahue CA et al (2003) Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res 63:4158-4166 (Pubitemid 36917941)
93. Shi H, Wei SH, Leu YW, Rahmatpanah F, Liu JC, Yan PS et al (2003) Triple analysis of the cancer epigenome: an integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation. Cancer Res 63:2164-2171 (Pubitemid 36538622)
94. Shibahara H, Tamada S, Goto M, Oda K, Nagino M, Nagasaka T et al (2004a) Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms. Am J Surg Pathol 28:327-338 (Pubitemid 38269566)
95. Shibahara H, Tamada S, Higashi M, Goto M, Batra SK, Hollingsworth MA et al (2004b) MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type. Hepatology 39:220-229 (Pubitemid 38461485)
96. Shinojima Y, Terui T, Hara H, Kimura M, Igarashi J, Wang X et al (2010) Identification and analysis of an early diagnostic marker for malignant melanoma: ZAR1 intra-genic differential methylation. J Dermatol Sci 59:98-106
97. Siedow A, Szyf M, Gratchev A, Kobalz U, Hanski ML, Bumke-Vogt C et al (2002) De novo expression of the Muc2 gene in pancreas carcinoma cells is triggered by promoter demethylation. Tumour Biol 23:54-60 (Pubitemid 34225022)
98. Singh AP, Chauhan SC, Bafna S, Johansson SL, Smith LM, Moniaux N et al (2006) Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas. Prostate 66:421-429 (Pubitemid 43348735)
99. Suh SO, Chen Y, Zaman MS, Hirata H, Yamamura S, Shahryari V et al. (2011) MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer. Carcinogenesis, published online 23 Feb
100. Sun W, Liu Y, Glazer CA, Shao C, Bhan S, Demokan S et al (2010) TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1alpha stabilization. Clin Cancer Res 16:857-866
101. Takao S, Uchikura K, Yonezawa S, Shinchi H, Aikou T (1999) Mucin core protein expression in extrahepatic bile duct carcinoma is associated with metastases to the liver and poor prognosis. Cancer 86:1966-1975
102. Tamada S, Goto M, Nomoto M, Nagata K, Shimizu T, Tanaka S et al (2002) Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas: its relationship with tumor progression and prognosis. Pathol Int 52:713-723 (Pubitemid 35472026)
103. Tamada S, Shibahara H, Higashi M, Goto M, Batra SK, Imai K et al (2006) MUC4 is a novel prognostic factor of extrahepatic bile duct carcinoma. Clin Cancer Res 12:4257-4264
104. Toribara NW, Roberton AM, Ho SB, Kuo WL, Gum E, Hicks JW et al (1993) Human gastric mucin. Identification of a unique species by expression cloning. J Biol Chem 268:5879-5885 (Pubitemid 23090922)
105. Tsutsumida H, Goto M, Kitajima S, Kubota I, Hirotsu Y, Wakimoto J et al (2007) MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma. Lung Cancer 55:195-203 (Pubitemid 46074231)
106. Utsunomiya T, Yonezawa S, Sakamoto H, Kitamura H, Hokita S, Aiko T et al (1998) Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients. Clin Cancer Res 4:2605-2614 (Pubitemid 28523486)
107. Van Seuningen I, Vincent A (2009) Mucins: a new family of epigenetic biomarkers in epithelial cancers. Expert Opinion 3:411-427
108. Van Seuningen I, Pigny P, Perrais M, Porchet N, Aubert JP (2001) Transcriptional regulation of the 11p15 mucin genes. Towards new biological tools in human therapy, in inflammatory diseases and cancer? Front Biosci 6:D1216-D1234
109. Velcich A, Yang W, Heyer J, Fragale A, Nicholas C, Viani S et al (2002) Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295:1726-1729 (Pubitemid 34202910)
110. Vincent A, Perrais M, Desseyn JL, Aubert JP, Pigny P, Van Seuningen I (2007) Epigenetic regulation (DNA methylation, histone modifications) of the 11p15 mucin genes (MUC2, MUC5AC, MUC5B, MUC6) in epithelial cancer cells. Oncogene 26:6566-6576 (Pubitemid 47530602)
111. Vincent A, Ducourouble MP, Van Seuningen I (2008) Epigenetic regulation of the human mucin gene MUC4 in epithelial cancer cell lines involves both DNA methylation and histone modifications mediated by DNA methyltransferases and histone deacetylases. FASEB J 22:3035-3045
112. Wang RQ, Fang DC (2003) Alterations of MUC1 and MUC3 expression in gastric carcinoma: relevance to patient clinicopathological features. J Clin Pathol 56:378-384
113. White CL, Suto RK, Luger K (2001) Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions. EMBO J 20:5207-5218 (Pubitemid 32910915)
114. Williams SJ, McGuckin MA, Gotley DC, Eyre HJ, Sutherland GR, Antalis TM (1999) Two novel mucin genes down-regulated in colorectal cancer identified by differential display. Cancer Res 59:4083-4089 (Pubitemid 29393581)
115. Wolff EM, Byun HM, Han HF, Sharma S, Nichols PW, Siegmund KD et al (2010) Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer. PLoS Genet 6:e1000917
116. Wolffe AP, Matzke MA (1999) Epigenetics: regulation through repression. Science 286:481-486
117. Yamada N, Hamada T, Goto M, Tsutsumida H, Higashi M, Nomoto M et al (2006) MUC2 expression is regulated by histone H3 modification and DNA methylation in pancreatic cancer. Int J Cancer 119:1850-1857 (Pubitemid 44356842)
118. Yamada N, Nishida Y, Tsutsumida H, Hamada T, Goto M, Higashi M et al (2008) MUC1 expression is regulated by DNA methylation and histone H3 lysine 9 modification in cancer cells. Cancer Res 68:2708-2716 (Pubitemid 351556268)
119. Yamada N, Nishida Y, Tsutsumida H, Goto M, Higashi M, Nomoto M et al (2009) Promoter CpG methylation in cancer cells contributes to the regulation of MUC4. Br J Cancer 100:344-351
120. Yamada N, Nishida Y, Yokoyama S, Tsutsumida H, Houjou I, Kitamoto S et al (2010) Expression of MUC5AC, an early marker of pancreatobiliary cancer, is regulated by DNA methylation in the distal promoter region in cancer cells. J Hepatobiliary Pancreat Sci 17:844-854
121. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N et al (1986) Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature 319:230-234 (Pubitemid 16128786)
122. Yamashita K, Yonezawa S, Tanaka S, Shirahama H, Sakoda K, Imai K et al (1993) Immunohistochemical study of mucin carbohydrates and core proteins in hepatolithiasis and cholangiocarcinoma. Int J Cancer 55:82-91 (Pubitemid 23261711)
123. Yin BW, Lloyd KO (2001) Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16. J Biol Chem 276:27371-27375
124. Yonezawa S, Sato E (1997) Expression of mucin antigens in human cancers and its relationship with malignancy potential. Pathol Int 47:813-830 (Pubitemid 28087380)
125. Yonezawa S, Sueyoshi K, Nomoto M, Kitamura H, Nagata K, Arimura Y et al (1997) MUC2 gene expression is found in noninvasive tumors but not in invasive tumors of the pancreas and liver: its close relationship with prognosis of the patients. Hum Pathol 28:344-352 (Pubitemid 27106088)
126. Yonezawa S, Horinouchi M, Osako M, Kubo M, Takao S, Arimura Y et al (1999) Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor. Pathol Int 49:45-54 (Pubitemid 29421947)
127. Yonezawa S, Goto M, Yamada N, Higashi M, Nomoto M (2008) Expression profiles of MUC1, MUC2, and MUC4 mucins in human neoplasms and their relationship with biological behavior. Proteomics 8:3329-3341
128. Yonezawa S, Higashi M, Yamada N, Yokoyama S, Goto M (2010) Significance of mucin expression in pancreatobiliary neoplasms. J Hepatobiliary Pancreat Sci 17:108-124
129. Zen Y, Sasaki M, Fujii T, Chen TC, Chen MF, Yeh TS et al (2006) Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct-an immunohistochemical study of 110 cases of hepatolithiasis. J Hepatol 44:350-358 (Pubitemid 43069217)
130. Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N et al (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA 105:7004-7009 (Pubitemid 351754520)
131. Zhu Y, Zhang JJ, Zhu R, Liang WB, Gao WT, Yu JB et al. (2010) The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma. Med Oncol, published online 5 Oct
132. Zilberman D, Henikoff S (2007) Genome-wide analysis of DNA methylation patterns. Development 134:3959-3965 (Pubitemid 350269413)
133. Zrihan-Licht S, Weiss M, Keydar I, Wreschner DH (1995) DNA methylation status of the MUC1 gene coding for a breast-cancerassociated protein. Int J Cancer 62:245-251