Melanoma epigenetics: Novel mechanisms, markers, and medicines

Laboratory Investigation

Volumn 94, Issue 8, 2014, Pages 822-838

  Lee, Jonathan J ^a   Murphy, George F ^a   Lian, Christine G ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; 5 HYDROXYMETHYLCYTOSINE; AZACITIDINE; BIOLOGICAL MARKER; CARRIER PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 2A; DNA BASE; DNA METHYLTRANSFERASE; HISTONE; HISTONE DEACETYLASE; HISTONE METHYLTRANSFERASE; IPILIMUMAB; ISOCITRATE DEHYDROGENASE; MICRORNA; PANOBINOSTAT; PEGINTERFERON; RECOMBINANT ALPHA2B INTERFERON; ROMIDEPSIN; SALINOSPORAMIDE A; SUCCINATE DEHYDROGENASE; TEMOZOLOMIDE; THYMINE DNA GLYCOSYLASE; UNTRANSLATED RNA; VORINOSTAT;

APOPTOSIS; ARTICLE; BREAST CANCER; CANCER DIAGNOSIS; CANCER INCIDENCE; CANCER MORTALITY; CANCER PROGNOSIS; CANCER STEM CELL; CARCINOGENESIS; CELL CYCLE PROGRESSION; CELL RENEWAL; CHEMOSENSITIZATION; CHROMATIN STRUCTURE; CHROMOSOMAL INSTABILITY; CUTANEOUS MELANOMA; CUTANEOUS T CELL LYMPHOMA; DEMETHYLATION; DIAGNOSTIC VALUE; DNA METHYLATION; DNA SEQUENCE; DYSPLASTIC NEVUS; EPIGENETICS; EXCISION REPAIR; GASTROINTESTINAL STROMAL TUMOR; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE MUTATION; GENETIC MARKER; HETEROCHROMATIN; HISTONE MODIFICATION; HUMAN; HYDROXYMETHYLATION; LIVER CELL CARCINOMA; MALIGNANT TRANSFORMATION; MELANOMA CELL; METASTATIC MELANOMA; MOUTH SQUAMOUS CELL CARCINOMA; MYELODYSPLASTIC SYNDROME; NEVUS; NONHUMAN; PATHOLOGY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHENOTYPIC VARIATION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN PROCESSING; RNA TRANSLATION;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL MARKERS; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; DNA, NEOPLASM; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTONE DEACETYLASE INHIBITORS; HISTONES; HUMANS; MELANOMA; MICRORNAS; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; NEOPLASM PROTEINS; PROTEIN PROCESSING, POST-TRANSLATIONAL; RNA INTERFERENCE; RNA, NEOPLASM; RNA, UNTRANSLATED; SKIN; SKIN NEOPLASMS;

EID: 84905196758     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2014.87     Document Type: Article

References (190)

1. Holliday R. The inheritance of epigenetic defects. Science 1987;238: 163-170.
2. Holliday R. Epigenetics: a historical overview. Epigenetics 2006;1:76-80.
3. Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell 2007;128:635-638.
4. Riggs AD. X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 1975;14:9-25.
5. Holliday R, Pugh JE. DNA modification mechanisms and gene activity during development. Science 1975;187:226-232.
6. Lister R, Ecker JR. Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res 2009;19:959-966.
7. Guibert S, Weber M. Functions of DNA methylation and hydroxyme-thylation in mammalian development. Curr Top Dev Biol 2013;104: 47-83.
8. Bird AP. CpG-rich islands and the function of DNA methylation. Nature 1986;321:209-213.
9. Fatemi M, Pao MM, Jeong S, et al. Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level. Nucleic Acids Res 2005;33:e176.
10. Maunakea AK, Nagarajan RP, Bilenky M, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 2010;466:253-257.
11. Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009;462:315-322.
12. Catoni GL. S-adenosylmethionine; a new intermediate formed enzy-matically from L-methionine and adenosinetriphosphate. J Biol Chem 1953;204:403-416.
13. Sen GL, Reuter JA, Webster DE, et al. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature 2010;463:563-567.
14. Okano M, Bell DW, Haber DA, et al. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 1999;99:247-257.
15. Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 2013;502:472-479.
16. Wyatt GR, Cohen SS. A new pyrimidine base from bacteriophage nucleic acids. Nature 1952;170:1072-1073.
17. Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 2009;324:930-935.
18. Cortellino S, Xu J, Sannai M, et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 2011;146:67-79.
19. He YF, Li BZ, Li Z, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 2011;333: 1303-1307.
20. Haffner MC, Chaux A, Meeker AK, et al. Global 5-hydroxymethyl-cytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers. Oncotarget 2011;2:627-637.
21. Ito S, D'Alessio AC, Taranova OV, et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010;466:1129-1133.
22. Koh KP, Yabuuchi A, Rao S, et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 2011;8:200-213.
23. Williams K, Christensen J, Pedersen MT, et al. TET1 and hydroxymethyl-cytosine in transcription and DNA methylation fidelity. Nature 2011;473:343-348.
24. Williams K, Christensen J, Helin K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep 2012;13:28-35.
25. Abdel-Wahab O, Mullally A, Hedvat C, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood 2009; 114:144-147.
26. Moran-Crusio K, Reavie L, Shih A, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 2011;20:11-24.
27. Sun M, Song CX, Huang H, et al. HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis. Proc Natl Acad Sci USA 2013;110:9920-9925.
28. Jawert F, Hasseus B, Kjeller G, et al. Loss of 5-hydroxymethylcytosine and TET2 in oral squamous cell carcinoma. Anticancer Res 2013;33: 4325-4328.
29. Mason EF, Hornick JL. Succinate dehydrogenase deficiency is associated with decreased 5-hydroxymethylcytosine production in gastrointestinal stromal tumors: implications for mechanisms of tumorigenesis. Mod Pathol 2013;26:1492-1497.
30. Liu C, Liu L, Chen X, et al. Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1. PLoS One 2013;8:e62828.
31. Song SJ, Poliseno L, Song MS, et al. MicroRNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling. Cell 2013;154:311-324.
32. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009;360:765-773.
33. Yen KE, Bittinger MA, Su SM, et al. Mutations: biomarker and therapeutic opportunities. Oncogene 2010;29:6409-6417.
34. Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 2011;19:17-30.
35. Killian JK, Kim SY, Miettinen M, et al. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov 2013;3:648-657.
36. Kouzarides T. Chromatin modifications and their function. Cell 2007;128:693-705.
37. Tan M, Luo H, Lee S, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 2011;146:1016-1028.
38. Shi Y, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004;119:941-953.
39. Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell 2007;128:707-719.
40. Dobosy JR, Selker EU. Emerging connections between DNA methylation and histone acetylation. Cell Mol Life Sci 2001;58: 721-727.
41. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004;4:143-153.
42. Nguyen CT, Weisenberger DJ, Velicescu M, et al. 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 2002; 62:6456-6461.
43. Seligson DB, Horvath S, Shi T, et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature 2005;435: 1262-1266.
44. Schwartz YB, Pirrotta V. Polycomb silencing mechanisms and the management of genomic programmes. Nat Rev Genet 2007;8:9-22.
45. Schwartz YB, Pirrotta V. A new world of Polycombs: unexpected partnerships and emerging functions. Nat Rev Genet 2013;14:853-864.
46. Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol 2013;26:155-165.
47. Moulton T, Crenshaw T, Hao Y, et al. Epigenetic lesions at the H19 locus in Wilms' tumour patients. Nat Genet 1994;7:440-447.
48. Bartolomei MS, Zemel S, Tilghman SM. Parental imprinting of the mouse H19 gene. Nature 1991;351:153-155.
49. Costa FF. Non-coding RNAs: lost in translation? Gene 2007;386:1-10.
50. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009;136:215-233.
51. Costa FF. Non-coding RNAs: new players in eukaryotic biology. Gene 2005;357:83-94.
52. Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol 2011;21:354-361.
53. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983;301:89-92.
54. Kim YI, Giuliano A, Hatch KD, et al. Global DNA hypomethylation increases progressively in cervical dysplasia and carcinoma. Cancer 1994;74:893-899.
55. Cravo M, Pinto R, Fidalgo P, et al. Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma. Gut 1996;39:434-438.
56. Soares J, Pinto AE, Cunha CV, et al. Global DNA hypomethylation in breast carcinoma: correlation with prognostic factors and tumor progression. Cancer 1999;85:112-118.
57. Karpf AR, Matsui S. Genetic disruption of cytosine DNA methyltrans-ferase enzymes induces chromosomal instability in human cancer cells. Cancer Res 2005;65:8635-8639.
58. Herman JG, Latif F, Weng Y, et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 1994;91:9700-9704.
59. Yoshiura K, Kanai Y, Ochiai A, et al. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA 1995;92:7416-7419.
60. Fraga MF, Herranz M, Espada J, et al. A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res 2004;64:5527-5534.
61. Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA 1999;96: 8681-8686.
62. Tanemura A, Terando AM, Sim MS, et al. CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res 2009;15:1801-1807.
63. Patino WD, Susa J. Epigenetics of cutaneous melanoma. Adv Dermatol 2008;24:59-70.
64. Straume O, Smeds J, Kumar R, et al. Significant impact of promoter hypermethylation and the 540 C4T polymorphism of CDKN2A in cutaneous melanoma of the vertical growth phase. Am J Pathol 2002;161:229-237.
65. Bishop JN, Harland M, Randerson-Moor J, et al. Management of familial melanoma. Lancet Oncol 2007;8:46-54.
66. Walker GJ, Flores JF, Glendening JM, et al. Virtually 100% of melanoma cell lines harbor alterations at the DNA level within CDKN2A, CDKN2B, or one of their downstream targets. Genes Chromosomes Cancer 1998;22:157-163.
67. Hoon DS, Spugnardi M, Kuo C, et al. Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients. Oncogene 2004;23:4014-4022.
68. Xu XC. Tumor-suppressive activity of retinoic acid receptor-beta in cancer. Cancer Lett 2007;253:14-24.
69. Sigalotti L, Covre A, Fratta E, et al. Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies. J Transl Med 2010;8:56.
70. Paz MF, Fraga MF, Avila S, et al. A systematic profile of DNA methylation in human cancer cell lines. Cancer Res 2003;63:1114-1121.
71. Lian CG, Xu Y, Ceol C, et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 2012;150:1135-1146.
72. Gambichler T, Sand M, Skrygan M. Loss of 5-hydroxymethylcytosine and ten-eleven translocation 2 protein expression in malignant melanoma. Melanoma Res 2013;23:218-220.
73. Uchiyama R, Uhara H, Uchiyama A, et al. 5-Hydroxymethylcytosine as a useful marker to differentiate between malignant melanomas and benign melanocytic nevi. J Dermatol Sci 2014;73:161-163.
74. Larson AR, Dresser KA, Zhan Q, et al. Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors. Mod Pathol; advance online publication, 3 January 2014; doi:10.1038/modpathol.2013. 224 (e-pub ahead of print).
75. Jin SG, Jiang Y, Qiu R, et al. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. Cancer Res 2011;71:7360-7365.
76. Shibata T, Kokubu A, Miyamoto M, et al. Mutant IDH1 confers an in vivo growth in a melanoma cell line with BRAF mutation. Am J Pathol 2011;178:1395-1402.
77. Preston BD, Albertson TM, Herr AJ. DNA replication fidelity and cancer. Semin Cancer Biol 2010;20:281-293.
78. Song J, Teplova M, Ishibe-Murakami S, et al. Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science 2012;335:709-712.
79. Matje DM, Zhou H, Smith DA, et al. Enzyme-promoted base flipping controls DNA methylation fidelity. Biochemistry 2013;52:1677-1685.
80. Borgaro JG, Benner N, Zhu Z. Fidelity index determination of DNA methyltransferases. PLoS One 2013;8:e63866.
81. Greenberg ES, Chong KK, Huynh KT, et al. Epigenetic biomarkers in skin cancer. Cancer Lett 2014;342:170-177.
82. Florenes VA, Skrede M, Jorgensen K, et al. Deacetylase inhibition in malignant melanomas: impact on cell cycle regulation and survival. Melanoma Res 2004;14:173-181.
83. Zhang XD, Gillespie SK, Borrow JM, et al. The histone deacetylase inhibitor suberic bishydroxamate regulates the expression of multiple apoptotic mediators and induces mitochondria-dependent apoptosis of melanoma cells. Mol Cancer Ther 2004;3:425-435.
84. Ye Y, Jin L, Wilmott JS, et al. PI(4, 5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma. Nat Commun 2013;4:1508.
85. Bachmann IM, Halvorsen OJ, Collett K, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 2006;24:268-273.
86. McHugh JB, Fullen DR, Ma L, et al. Expression of polycomb group protein EZH2 in nevi and melanoma. J Cutan Pathol 2007;34:597-600.
87. Ceol CJ, Houvras Y, Jane-Valbuena J, et al. The histone methyltrans-ferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature 2011;471:513-517.
88. Alharbi RA, Pettengell R, Pandha HS, et al. The role of HOX genes in normal hematopoiesis and acute leukemia. Leukemia 2013;27:1000-1008.
89. Karram S, Novy M, Saroufim M, et al. Predictors of BRAF mutation in melanocytic nevi: analysis across regions with different UV radiation exposure. Am J Dermatopathol 2013;35:412-418.
90. Rodriguez-Paredes M, Martinez de Paz A, Simo-Riudalbas L, et al. Gene amplification of the histone methyltransferase SETDB1 contributes to human lung tumorigenesis. Oncogene 2013;33:2807-2813.
91. Bennett PE, Bemis L, Norris DA, et al. miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma. Physiol Genom 2013;45:1049-1059.
92. Liu S, Tetzlaff MT, Cui R, et al. MiR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1. Am J Pathol 2012;181:1823-1835.
93. Ringrose L, Paro R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu Rev Genet 2004;38: 413-443.
94. Jacobs JJ, Scheijen B, Voncken JW, et al. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev 1999;13:2678-2690.
95. Tao ZH, Wan JL, Zeng LY, et al. MiR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma. The J Exp Med 2013;210:789-803.
96. van Kempen LC, van den Hurk K, Lazar V, et al. Loss of microRNA-200a and c, and microRNA-203 expression at the invasive front of primary cutaneous melanoma is associated with increased thickness and disease progression. Virchows Arch 2012;461:441-448.
97. Jin L, Hu WL, Jiang CC, et al. MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma. Proc Natl Acad Sci USA 2011;108:15840-15845.
98. Satzger I, Mattern A, Kuettler U, et al. MicroRNA-21 is upregulated in malignant melanoma and influences apoptosis of melanocytic cells. Exp Dermatol 2012;21:509-514.
99. Streicher KL, Zhu W, Lehmann KP, et al. A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth. Oncogene 2012;31:1558-1570.
100. Pencheva N, Tran H, Buss C, et al. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 2012;151:1068-1082.
101. Tang L, Zhang W, Su B, et al. Long noncoding RNA HOTAIR is associated with motility, invasion, and metastatic potential of metastatic melanoma. Biomed Res Int 2013;2013:251098.
102. Engreitz JM, Pandya-Jones A, McDonel P, et al. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 2013;341:1237973.
103. Khaitan D, Dinger ME, Mazar J, et al. The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res 2011;71:3852-3862.
104. Wu CF, Tan GH, Ma CC, et al. The non-coding RNA llme23 drives the malignant property of human melanoma cells. J Genet Genom 2013;40:179-188.
105. Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006;66:9339-9344.
106. Bruce WR, Van Der Gaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature 1963;199:79-80.
107. Park CH, Bergsagel DE, McCulloch EA. Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst 1971;46:411-422.
108. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003;100:3983-3988.
109. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396-401.
110. O'Brien CA, Pollett A, Gallinger S, et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106-110.
111. Schatton T, Murphy GF, Frank NY, et al. Identification of cells initiating human melanomas. Nature 2008;451:345-349.
112. Girouard SD, Murphy GF. Melanoma stem cells: not rare, but well done. Lab Invest 2011;91:647-664.
113. Ito K, Bernardi R, Pandolfi PP. A novel signaling network as a critical rheostat for the biology and maintenance of the normal stem cell and the cancer-initiating cell. Curr Opin Genet Dev 2009;19: 51-59.
114. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 2008;8:755-768.
115. White RA, Neiman JM, Reddi A, et al. Epithelial stem cell mutations that promote squamous cell carcinoma metastasis. J Clin Invest 2013; 123:4390-4404.
116. Caramel J, Papadogeorgakis E, Hill L, et al. A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell 2013;24:466-480.
117. Concepcion Garrido M, Requena L, Kutzner H, et al. Desmoplastic melanoma: expression of epithelial-mesenchymal transition-related proteins. Am J Dermatopathol 2013;36:238-242.
118. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009;9:265-273.
119. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science 2011;331:1559-1564.
120. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006;127:679-695.
121. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008;133:704-715.
122. Miller AJ, Mihm Jr MC. Melanoma. N Engl J Med 2006;355:51-65.
123. Alexaki VI, Javelaud D, Van Kempen LC, et al. GLI2-mediated melanoma invasion and metastasis. J Natl Cancer Inst 2010;102: 1148-1159.
124. Danen EH, de Vries TJ, Morandini R, et al. E-cadherin expression in human melanoma. Melanoma Res 1996;6:127-131.
125. Hsu MY, Wheelock MJ, Johnson KR, et al. Shifts in cadherin profiles between human normal melanocytes and melanomas. J Invest Dermatol 1996;1:188-194.
126. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2:442-454.
127. Danen EH, Ten Berge PJ, Van Muijen GN, et al. Emergence of alpha 5 beta 1 fibronectin-and alpha v beta 3 vitronectin-receptor expression in melanocytic tumour progression. Histopathology 1994;24: 249-256.
128. Hofmann UB, Westphal JR, Waas ET, et al. Coexpression of integrin alpha(v)beta3 and matrix metalloproteinase-2 (MMP-2) coincides with MMP-2 activation: correlation with melanoma progression. J Invest Dermatol 2000;115:625-632.
129. Liang Y, Jansen M, Aronow B, et al. The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice. Nat Genet 2007;39:178-188.
130. Liang Y, Van Zant G. Aging stem cells, latexin, and longevity. Exp Cell Res 2008;314:1962-1972.
131. Muthusamy V, Premi S, Soper C, et al. The hematopoietic stem cell regulatory gene latexin has tumor-suppressive properties in malignant melanoma. J Invest Dermatol 2013;133:1827-1833.
132. Roesch A, Fukunaga-Kalabis M, Schmidt EC, et al. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 2010;141:583-594.
133. Iwase S, Lan F, Bayliss P, et al. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 2007;128:1077-1088.
134. Roesch A, Becker B, Meyer S, et al. Retinoblastoma-binding protein 2-homolog 1: a retinoblastoma-binding protein downregulated in malignant melanomas. Mod Pathol 2005;18:1249-1257.
135. Scibetta AG, Santangelo S, Coleman J, et al. Functional analysis of the transcription repressor PLU-1/JARID1B. Mol Cell Biol 2007;27: 7220-7235.
136. Krivtsov AV, Armstrong SA. MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 2007;7: 823-833.
137. Roesch A, Becker B, Schneider-Brachert W, et al. Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells. J Invest Dermatol 2006;126:1850-1859.
138. Yamane K, Tateishi K, Klose RJ, et al. PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol Cell 2007;25:801-812.
139. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-297.
140. He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature 2005;435:828-833.
141. Gregory PA, Bracken CP, Bert AG, et al. MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle 2008;7: 3112-3118.
142. Park SM, Gaur AB, Lengyel E, et al. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008;22:894-907.
143. Shimono Y, Zabala M, Cho RW, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 2009;138: 592-603.
144. Liu S, Kumar SM, Lu H, et al. MicroRNA-9 up-regulates E-cadherin through inhibition of NF-kappaB1-Snail1 pathway in melanoma. J Pathol 2012;226:61-72.
145. Song SJ, Pandolfi P. MiR-22 in tumorigenesis. Cell Cycle 2014;13: 11-12.
146. Song SJ, Ito K, Ala U, et al. The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell 2013;13:87-101.
147. Sigalotti L, Fratta E, Bidoli E, et al. Methylation levels of the 'long interspersed nucleotide element-1' repetitive sequences predict survival of melanoma patients. J Transl Med 2011;9:78.
148. Marini A, Mirmohammadsadegh A, Nambiar S, et al. Epigenetic inactivation of tumor suppressor genes in serum of patients with cutaneous melanoma. J Invest Dermatol 2006;126:422-431.
149. Hanna JA, Hahn L, Agarwal S, et al. In situ measurement of miR-205 in malignant melanoma tissue supports its role as a tumor suppressor microRNA. Lab Invest 2012;92:1390-1397.
150. Liu S, Tetzlaff MT, Liu A, et al. Loss of microRNA-205 expression is associated with melanoma progression. Lab Invest 2012;92: 1084-1096.
151. Nguyen T, Kuo C, Nicholl MB, et al. Downregulation of microRNA-29c is associated with hypermethylation of tumor-related genes and disease outcome in cutaneous melanoma. Epigenetics 2011;6: 388-394.
152. Asangani IA, Harms PW, Dodson L, et al. Genetic and epigenetic loss of microRNA-31 leads to feed-forward expression of EZH2 in melanoma. Oncotarget 2012;3:1011-1025.
153. Luo C, Tetteh PW, Merz PR, et al. MiR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes. J Invest Dermatol 2013;133:768-775.
154. Kanemaru H, Fukushima S, Yamashita J, et al. The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci 2011;61:187-193.
155. Friedman EB, Shang S, de Miera EV, et al. Serum microRNAs as biomarkers for recurrence in melanoma. J Transl Med 2012; 10:155.
156. McMillan TJ, Hart IR. Enhanced experimental metastatic capacity of a murine melanoma following pre-treatment with anticancer drugs. Clin Exp Metast 1986;4:285-292.
157. Woods DM, Woan K, Cheng F, et al. The antimelanoma activity of the histone deacetylase inhibitor panobinostat (LBH589) is mediated by direct tumor cytotoxicity and increased tumor immunogenicity. Melanoma Res 2013;23:341-348.
158. Weber J, Salgaller M, Samid D, et al. Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2'-deoxycytidine. Cancer Res 1994;54:1766-1771.
159. Serrano A, Garcia A, Abril E, et al. Methylated CpG points identified within MAGE-1 promoter are involved in gene repression. Int J Cancer 1996;68:464-470.
160. De Smet C, De Backer O, Faraoni I, et al. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA 1996;93:7149-7153.
161. Vo DD, Prins RM, Begley JL, et al. Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive use of the histone deacetylase inhibitor LAQ824. Cancer Res 2009;69:8693-8699.
162. Weber JS, Kudchadkar RR, Yu B, et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or-naive melanoma. J Clin Oncol 2013;31:4311-4318.
163. Kruit WH, Suciu S, Dreno B, et al. Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma. J Clin Oncol 2013;31:2413-2420.
164. Jazirehi AR, Arle D. Epigenetic regulation of the TRAIL/Apo2L apoptotic pathway by histone deacetylase inhibitors: an attractive approach to bypass melanoma immunotherapy resistance. Am J Clin Exp Immunol 2013;2:55-74.
165. Verbeek B, Southgate TD, Gilham DE, et al. O6-methylguanine-DNA methyltransferase inactivation and chemotherapy. Br Med Bull 2008; 85:17-33.
166. Christmann M, Pick M, Lage H, et al. Acquired resistance of melanoma cells to the antineoplastic agent fotemustine is caused by reactivation of the DNA repair gene MGMT. Int J Cancer 2001; 92:123-129.
167. Tawbi HA, Beumer JH, Tarhini AA, et al. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Ann Oncol 2013;24:1112-1119.
168. Sato Y, Marzese DM, Ohta K, et al. Epigenetic regulation of REG1A and chemosensitivity of cutaneous melanoma. Epigenetics 2013;8: 1043-1052.
169. Soengas MS, Capodieci P, Polsky D, et al. Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 2001;409: 207-211.
170. Fulda S, Kufer MU, Meyer E, et al. Sensitization for death receptor-or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene 2001;20:5865-5877.
171. Valentini A, Gravina P, Federici G, et al. Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells. Cancer Biol Ther 2007;6:185-191.
172. Daud AI, Dawson J, DeConti RC, et al. Potentiation of a topoisomerase I inhibitor, karenitecin, by the histone deacetylase inhibitor valproic acid in melanoma: translational and phase I/II clinical trial. Clin Cancer Res 2009;15:2479-2487.
173. Munshi A, Kurland JF, Nishikawa T, et al. Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity. Clin Cancer Res 2005;11:4912-4922.
174. Munshi A, Tanaka T, Hobbs ML, et al. A histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci. Mol Cancer Ther 2006;5:1967-1974.
175. Lian CG, Mihm MC, Pierard G, et al. Skin cancer. In: Stewart BW, Wild CP (eds). World Cancer Report 2014. Lyon, France: International Agency for Research on Cancer, WHO, 2014.
176. Segura MF, Fontanals-Cirera B, Gaziel-Sovran A, et al. BRD4 sustains melanoma proliferation and represents a new target for epigenetic therapy. Cancer Res 2013;73:6264-6276.
177. Matzuk MM, McKeown MR, Filippakopoulos P, et al. Small-molecule inhibition of BRDT for male contraception. Cell 2012;150:673-684.
178. Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer 2012;12:465-477.
179. Müller DW, Bosserhoff AK. Integrin beta 3 expression is regulated by let-7a miRNA in malignant melanoma. Oncogene 2008;27:6698-6706.
180. Bhattacharya A, Schmitz U, Wolkenhauer O, et al. Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma. Oncogene 2013;32:3175-3183.
181. Felicetti F, Errico MC, Bottero L, et al. The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res 2008;68:2745-2754.
182. Igoucheva O, Alexeev V. MicroRNA-dependent regulation of cKit in cutaneous melanoma. Biochem Biophys Res Commun 2009;379: 790-794.
183. Chen J, Zhang X, Lentz C, et al. miR-193b Regulates Mcl-1 in Melanoma. Am J Pathol 2011;179:2162-2168.
184. Penna E, Orso F, Cimino D, et al. MicroRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C. EMBO J 2011;30:1990-2007.
185. Dar AA, Majid S, de Semir D, et al. MiRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. J Biol Chem 2011;286:16606-16614.
186. Reuland SN, Smith SM, Bemis LT, et al. MicroRNA-26a is strongly downregulated in melanoma and induces cell death through repression of silencer of death domains (SODD). J Invest Dermatol 2013;133:1286-1293.
187. Lodygin D, Tarasov V, Epanchintsev A, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle 2008;7:2591-2600.
188. Kappelmann M, Kuphal S, Meister G, et al. MicroRNA miR-125b controls melanoma progression by direct regulation of c-Jun protein expression. Oncogene 2013;32:2984-2991.
189. Dar AA, Majid S, Rittsteuer C, et al. The role of miR-18b in MDM2-p53 pathway signaling and melanoma progression. J Natl Cancer Inst 2013;105:433-442.
190. Wang HF, Chen H, Ma MW, et al. MiR-573 regulates melanoma progression by targeting the melanoma cell adhesion molecule. Oncol Rep 2013;30:520-526.