TY - JOUR
T1 - CpG island methylation profiling in human melanoma cell lines
AU - Tellez, Carmen S.
AU - Shen, Lanlan
AU - Estécio, Marcos R.H.
AU - Jelinek, Jaroslav
AU - Gershenwald, Jeffrey E.
AU - Issa, Jean Pierre J.
PY - 2009/6
Y1 - 2009/6
N2 - A better understanding of key molecular changes during the pathogenesis of melanoma could impact strategies to reduce mortality from this cancer. Two epigenetic events involved in the pathogenesis of cancer are hypermethylation of tumor-suppressor gene promoters associated with transcriptional repression and hypomethylation associated with gene reexpression and genomic instability. We analyzed 16 melanoma cell lines for aberrant hypermethylation of 15 cancer-linked genes (ERα, MGMT, RARβ2, RIL, RASSF1A, PAX7, PGRβ, PAX2, NKX2-3, OLIG2, HAND1, ECAD, CDH13, MLH1, and p16) and hypomethylation of two genes (MAGEA1, maspin) and two repetitive sequences (LINE-1 and Alu) using pyrosequencing. We observed hypermethylation of ERα in 50% of the cell lines, MGMT (50%), RARβ2 (44%), RIL (88%), RASSF1A (69%), PAX7 (31%), PGRβ (56%), PAX2 (38%), NKX2-3 (63%), OLIG2 (63%), HAND1 (63%), ECAD (88%), CDH13 (44%), MLH1 (0%), and p16 (6%). In human melanoma cell lines, hypomethylation of MAGEA1 (44%), maspin (25%), LINE-1 (75%), and Alu (13%) is frequently observed. We analyzed a panel of cell lines for BRAF V600E and NRAS codon 61 mutations. In melanoma cell lines, the BRAF and NRAS mutations had no association with aberrant methylation. We found that the cumulative aberrant hypermethylation of the gene promoters was correlated with the level of global DNA methylation. We conclude that aberrant hypermethylation, is frequent in melanoma cell lines, directly correlated with global DNA methylation, and independent of BRAF and NRAS mutations.
AB - A better understanding of key molecular changes during the pathogenesis of melanoma could impact strategies to reduce mortality from this cancer. Two epigenetic events involved in the pathogenesis of cancer are hypermethylation of tumor-suppressor gene promoters associated with transcriptional repression and hypomethylation associated with gene reexpression and genomic instability. We analyzed 16 melanoma cell lines for aberrant hypermethylation of 15 cancer-linked genes (ERα, MGMT, RARβ2, RIL, RASSF1A, PAX7, PGRβ, PAX2, NKX2-3, OLIG2, HAND1, ECAD, CDH13, MLH1, and p16) and hypomethylation of two genes (MAGEA1, maspin) and two repetitive sequences (LINE-1 and Alu) using pyrosequencing. We observed hypermethylation of ERα in 50% of the cell lines, MGMT (50%), RARβ2 (44%), RIL (88%), RASSF1A (69%), PAX7 (31%), PGRβ (56%), PAX2 (38%), NKX2-3 (63%), OLIG2 (63%), HAND1 (63%), ECAD (88%), CDH13 (44%), MLH1 (0%), and p16 (6%). In human melanoma cell lines, hypomethylation of MAGEA1 (44%), maspin (25%), LINE-1 (75%), and Alu (13%) is frequently observed. We analyzed a panel of cell lines for BRAF V600E and NRAS codon 61 mutations. In melanoma cell lines, the BRAF and NRAS mutations had no association with aberrant methylation. We found that the cumulative aberrant hypermethylation of the gene promoters was correlated with the level of global DNA methylation. We conclude that aberrant hypermethylation, is frequent in melanoma cell lines, directly correlated with global DNA methylation, and independent of BRAF and NRAS mutations.
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U2 - 10.1097/CMR.0b013e32832b274e
DO - 10.1097/CMR.0b013e32832b274e
M3 - Article
C2 - 19441164
AN - SCOPUS:67849109939
SN - 0960-8931
VL - 19
SP - 146
EP - 155
JO - Melanoma research
JF - Melanoma research
IS - 3
ER -