Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 133, Issue 5, Pages 1278-1285Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2012.493
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Funding
- Barts and the London Charity
- Brain Tumor Research Charity (BTRC)
- Leng Foundation
- Medical Research Council
- Tayside Tissue Bank
- MRC [G0600450] Funding Source: UKRI
- Cancer Research UK [13044] Funding Source: researchfish
- Medical Research Council [G0600450] Funding Source: researchfish
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Transcriptional silencing of tissue factor pathway inhibitor 2 (TFPI2) occurs in several human tumors including melanoma. We investigated methylated TFPI2 as a biomarker of metastatic melanoma using qRT PCR to assess TFPI2 expression and pyrosequencing to analyze CpG island methylation in malignant melanoma cell lines, in benign nevi, in 112 primary and metastatic melanomas, and in serum from 6 healthy individuals and 35 patients: 20 patients with primary and 15 patients with metastatic melanoma. The TFPI2 CpG island is unmethylated in nevi but methylation is associated with metastatic melanoma. Circulating methylated TFPI2 DNA is undetectable in sera from healthy individuals and detectable in sera from patients with primary and metastatic melanomas, but the presence of methylated TFPI2 DNA in serum is strongly associated with metastatic disease (P<0.01). Detection of TFP/2-methylated DNA in the serum of patients with resected melanoma is a sensitive and specific biomarker of metastatic melanoma. Confirmation of our results in independent patient cohorts would encourage prospective evaluation as a biomarker of disease state.
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