Journal article
Aberrant CpG methylation of the TFAP2A gene constitutes a mechanism for loss of TFAP2A expression in human metastatic melanoma
Epigenetics, Vol.9(12), pp.1641-1647
12/02/2014
DOI: 10.4161/15592294.2014.988062
PMCID: PMC4622677
PMID: 25625848
Abstract
Metastatic melanoma is a deadly treatment-resistant form of skin cancer whose global incidence is on the rise. During melanocyte transformation and melanoma progression the expression profile of many genes changes. Among these, a gene implicated in several steps of melanocyte development, TFAP2A, is frequently silenced; however, the molecular mechanism of TFAP2A silencing in human melanoma remains unknown. In this study, we measured TFAP2A mRNA expression in primary human melanocytes compared to 11 human melanoma samples by quantitative real-time RT-PCR. In addition, we assessed CpG DNA methylation of the TFAP2A promoter in these samples using bisulfite sequencing. Compared to primary melanocytes, which showed high TFAP2A mRNA expression and no promoter methylation, human melanoma samples showed decreased TFAP2A mRNA expression and increased promoter methylation. We further show that increased CpG methylation correlates with decreased TFAP2A mRNA expression. Using The Cancer Genome Atlas, we further identified TFAP2A as a gene displaying among the most decreased expression in stage 4 melanomas vs. non-stage 4 melanomas, and whose CpG methylation was frequently associated with lack of mRNA expression. Based on our data, we conclude that TFAP2A expression in human melanomas can be silenced by aberrant CpG methylation of the TFAP2A promoter. We have identified aberrant CpG DNA methylation as an epigenetic mark associated with TFAP2A silencing in human melanoma that could have significant implications for the therapy of human melanoma using epigenetic modifying drugs.
Details
- Title: Subtitle
- Aberrant CpG methylation of the TFAP2A gene constitutes a mechanism for loss of TFAP2A expression in human metastatic melanoma
- Creators
- Andrea R Hallberg - Interdisciplinary Graduate Program in Molecular and Cellular Biology; Graduate College; The University of IowaSabine U Vorrink - Department of Radiation Oncology; Carver College of Medicine; The University of IowaDanielle R Hudachek - Summer Undergraduate Research Program, Interdisciplinary Graduate Program in Molecular and Cellular Biology, Graduate College; The University of IowaKimberly Cramer-Morales - Department of Radiation Oncology; Carver College of Medicine; The University of IowaMohammed M Milhem - Department of Internal Medicine; Carver College of Medicine; The University of IowaRobert A Cornell - Department of Anatomy and Cell Biology; Carver College of Medicine; The University of IowaFrederick E Domann - Department of Radiation Oncology; Carver College of Medicine; The University of Iowa
- Resource Type
- Journal article
- Publication Details
- Epigenetics, Vol.9(12), pp.1641-1647
- Publisher
- Taylor & Francis
- DOI
- 10.4161/15592294.2014.988062
- PMID
- 25625848
- PMCID
- PMC4622677
- ISSN
- 1559-2294
- eISSN
- 1559-2308
- Language
- English
- Date published
- 12/02/2014
- Academic Unit
- Anatomy and Cell Biology; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Orthopedics and Rehabilitation; Surgery; Radiation Oncology; Dental Research; Internal Medicine
- Record Identifier
- 9984025472802771
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