title: Methylated tissue factor pathway inhibitor 2 (TFPI2) DNA in serum is a biomarker of metastatic melanoma.
abstract: 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 TFPI2-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.
authors: Laboratory of Cancer Genetics and Translational Oncology, S Croce General Hospital, Cuneo, Italy.
authors: Cristiana
authors: C
authors: Lo Nigro
authors: Hexiao
authors: H
authors: Wang
authors: Angela
authors: A
authors: McHugh
authors: Laura
authors: L
authors: Lattanzio
authors: Rubeta
authors: R
authors: Matin
authors: Catherine
authors: C
authors: Harwood
authors: Nelofer
authors: N
authors: Syed
authors: Eleftheria
authors: E
authors: Hatzimichael
authors: Evangelos
authors: E
authors: Briasoulis
authors: Marco
authors: M
authors: Merlano
authors: Alan
authors: A
authors: Evans
authors: Alastair
authors: A
authors: Thompson
authors: Irene
authors: I
authors: Leigh
authors: Colin
authors: C
authors: Fleming
authors: Gareth J
authors: GJ
authors: Inman
authors: Charlotte
authors: C
authors: Proby
authors: Tim
authors: T
authors: Crook
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000097:blood / Q000175:diagnosis* / Q000556:secondary; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009506:Nevus / Q000097:blood / Q000175:diagnosis; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000556:secondary
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2