Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling

Liu, Suhu, Ren, Suping, Howell, Paul, Fodstad, Oystein and Riker, Adam I. (2008) Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling. Pigment Cell & Melanoma Research, 21 5: 545-558. doi:10.1111/j.1755-148X.2008.00484.x


Author Liu, Suhu
Ren, Suping
Howell, Paul
Fodstad, Oystein
Riker, Adam I.
Title Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling
Journal name Pigment Cell & Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
1755-148X
Publication date 2008-10
Sub-type Article (original research)
DOI 10.1111/j.1755-148X.2008.00484.x
Volume 21
Issue 5
Start page 545
End page 558
Total pages 14
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Abstract The inactivation of tumor-related genes through the aberrant methylation of promoter CpG islands is thought to contribute to tumor initiation and progression. We therefore investigated promoter methylation events involved in cutaneous melanoma by screening 30 genes of interest for evidence of promoter hypermethylation, examining 20 melanoma cell lines and 40 freshly procured melanoma samples. Utilizing quantitative methylation-specific PCR, we identified five genes (SOCS1, SOCS2, RAR-beta 2, TNFSF10C, and TNFSF10D) with hypermethylation frequencies ranging from 50% to 80% in melanoma cell lines as well as freshly procured tissue samples. Eighteen genes (LOX, RASSF1A, WFDC1, TM, APC, TFPI2, TNFSF10A, CDKN2A, MGMT, TIMP3, ASC, TPM1, IRF8, CIITA-PIV, CDH1, SYK, HOXB13, and DAPK1) were methylated at lower frequencies (2-30%). Two genes (CDKN1B and PTEN), previously reported as methylated in melanoma, and five other genes (RECK, IRF7, PAWR, TNFSF10B, and Rb) were not methylated in the samples screened here. Daughter melanoma cell lines showed identical methylation patterns when compared with original samples from which they were derived, as did synchronous metastatic lesions from the same patient. We identified four genes (TNFSF10C, TNFSF10D, LOX, and TPM1) that have never before been identified as hypermethylated in melanoma, with an overall methylation frequency of 60, 80, 50, and 10%, respectively, hypothesizing that these genes may play an important role in melanoma progression.
Keyword Melanoma
Promoter hypermethylation
Methylation profiling
Epigenetics
Quantitative methylationspecific PCR
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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