Cover Page The handle http://hdl.handle.net/1887/31819 holds various files of this Leiden University dissertation. Author: Gao, Linda Title: Promoter CpG island hypermethylation in the development of cutaneous melanoma Issue Date: 2015-02-04 Promoter CpG island hypermethylation in the development of cutaneous melanoma Proefschrift ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. P.F. van der Heijden, volgens besluit van het College voor Promoties te verdedigen op woensdag 4 februari 2015 klokke 16.15 uur door Linda Gao geboren te Beijing in 1984 Promoter CpG island hypermethylation in the development of cutaneous melanoma Financial support for the publication of this thesis was kindly provided by Galderma Benelux B.V. ISBN: 978-90-5335-987-7 Printed by Ridderprint B.V. Promoter CpG island hypermethylation in the development of cutaneous melanoma Proefschrift ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker, volgens besluit van het College voor Promoties te verdedigen op woensdag 4 februari 2015 klokke 16.15 uur door Linda Gao geboren te Beijing in 1984 Promotiecommissie Promotor Prof.dr. R. Willemze Co-promotor Dr. R. van Doorn Overige leden Prof.dr. J.J. van den Oord Catholic University Leuven (KU Leuven), Leuven, Belgium Prof.dr. W.J. Mooi VU University Medical Center (VUmc), Amsterdam Prof.dr.ir. S.M. van der Maarel Table of contents Abbreviations 9 Chapter 1 General introduction 11 Chapter 2 Genome-wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma 29 Pigment Cell & Melanoma Research 2013; 26(4):542-54 Chapter 3 Near-genomewide RNAi screening for regulators of BRAFV600E-induced senescence identifies RASEF, a gene epigenetically silenced in melanoma 61 Pigment Cell & Melanoma Research 2014; 27(4):640-52 Chapter 4 Promoter CpG island hypermethylation in dysplastic naevus and melanoma: CLDN11 as an epigenetic biomarker for malignancy 87 Journal of Investigative Dermatology 2014; 10.1038/jid.2014.270 Chapter 5 Genome-wide analysis of gene and protein expression of dysplastic naevus cells 109 Journal of Skin Cancer 2012; 2012: 981308 Chapter 6 Promoter CpG island hypermethylation of MCHR1 and SYNPO2 in primary cutaneous melanoma with metastatic behavior 131 Manuscript in preparation Chapter 7 Summary and Discussion Nederlandse samenvatting Curriculum vitae 145 161 167 Abbreviations AJCC American Joint Committee on Cancer BMCA bisulphite melting curve analysis BRAF B-Raf proto-oncogene, serine/threonine kinase BrdU 5-bromo-2´-deoxyuridine BSA bisulphite sequencing analysis C10rf106 chromosome 1 open reading frame 106 CDH1 cadherin 1, type 1, E-cadherin (epithelial) CDH11 cadherin 11, type 2, OB-cadherin (osteoblast) CDKN2A cyclin-dependent kinase inhibitor 2A CLDN11 claudin 11 CpG cytosine-phosphate-guanine dinucleotide in linear sequence CPSF6 cleavage and polyadenylation specific factor 6,68kDa D176A aspartic acid at amino acid 176 replaced by alanine, MAPK13 mutant DNMT DNA (cytosine-5-)-methyltransferase EFCAB1 EF-hand calcium binding domain 1 EZH2 enhancer of zeste 2 polycomb repressive complex 2 subunit F324S phenylalanine at amino acid 324 replaced by serine, MAPK13 mutant FAMMM familial atypical multiple mole melanoma HDAC histone deacetylase HIST1H3E histone cluster 1, H3e HOXA9 homeobox A9 LEP leptin MAGEA melanoma antigen family A MAGEB melanoma antigen family B MAPK13 mitogen-activated protein kinase 13 MBD methyl-CpG-binding domain proteins MCHR1 melanin-concentrating hormone receptor 1 MeCP2 methyl CpG binding protein 2 MeDIP methylated DNA immune precipitation MITF microphthalmia-associated transcription factor NRAS neuroblastoma RAS viral (v-ras) oncogene homolog OIS oncogene-induced senescence p38δ p38 MAP kinase protein, isoform δ PLEKHG6 pleckstrin homology domain containing, family G (with RhoGef domain) member 6 PPP1R3C protein phosphatase 1, regulatory subunit 3C RASEF RAS and EF-hand domain containing Rb retinoblastoma protein ROS reactive oxygen species SYNPO2 synaptopodin 2 (myopodin) TBP TATA box binding protein TIMP3 TIMP metallopeptidase inhibitor 3 TNM tumor depth (T), lymph node status (N), and distant metastasis (M) classification V600E valine at amino acid 600 replaced by glutamic acid, BRAF mutant 9 10
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