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Comprehensive DNA m...
Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma
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- Wouters, Jasper (author)
- Catholic University of Leuven,OncoMark Ltd
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- Vizoso, Miguel (author)
- Bellvitge Biomedical Research Institute
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- Martinez-Cardus, Anna (author)
- Bellvitge Biomedical Research Institute
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- Carmona, F Javier (author)
- Bellvitge Biomedical Research Institute
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- Govaere, Olivier (author)
- Catholic University of Leuven
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- Laguna, Teresa (author)
- Johannes-Gutenberg University Mainz,Bellvitge Biomedical Research Institute
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- Joseph, Jesuchristopher (author)
- OncoMark Ltd
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- Dynoodt, Peter (author)
- OncoMark Ltd
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- Aura, Claudia (author)
- Catholic University of Leuven
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- Foth, Mona (author)
- Cancer Research UK,OncoMark Ltd
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- Cloots, Roy (author)
- Maastricht University,OncoMark Ltd
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- van den Hurk, Karin (author)
- Maastricht University,OncoMark Ltd
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- Balint, Balazs (author)
- Bellvitge Biomedical Research Institute,OncoMark Ltd
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- Murphy, Ian G. (author)
- St Vincent's University Hospital
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- McDermott, Enda W. (author)
- St Vincent's University Hospital
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- Sheahan, Kieran (author)
- St Vincent's University Hospital
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- Jirström, Karin (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Nodin, Bjorn (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Mallya-Udupi, Girish (author)
- OncoMark Ltd
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- Van den Oord, Joost J (author)
- Catholic University of Leuven
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- Gallagher, William M (author)
- University College Dublin,OncoMark Ltd
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- Esteller, Manel (author)
- University of Barcelona,Bellvitge Biomedical Research Institute,Catalan Institution for Research and Advanced Studies
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(creator_code:org_t)
- 2017-06-05
- 2017
- English.
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:1, s. 1-16
- Related links:
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http://dx.doi.org/10... (free)
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https://bmcmedicine....
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Background: Cutaneous melanoma is the deadliest skin cancer, with an increasing incidence and mortality rate. Currently, staging of patients with primary melanoma is performed using histological biomarkers such as tumor thickness and ulceration. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, we aimed to identify novel biomarkers providing additional clinical information over current factors using unbiased genome-wide DNA methylation analyses. Methods: We performed a comprehensive DNA methylation analysis during all progression stages of melanoma using Infinium HumanMethylation450 BeadChips on a discovery cohort of benign nevi (n = 14) and malignant melanoma from both primary (n = 33) and metastatic (n = 28) sites, integrating the DNA methylome with gene expression data. We validated the discovered biomarkers in three independent validation cohorts by pyrosequencing and immunohistochemistry. Results: We identified and validated biomarkers for, and pathways involved in, melanoma development (e.g., HOXA9 DNA methylation) and tumor progression (e.g., TBC1D16 DNA methylation). In addition, we determined a prognostic signature with potential clinical applicability and validated PON3 DNA methylation and OVOL1 protein expression as biomarkers with prognostic information independent of tumor thickness and ulceration. Conclusions: Our data underscores the importance of epigenomic regulation in triggering metastatic dissemination through the inactivation of central cancer-related pathways. Inactivation of cell-adhesion and differentiation unleashes dissemination, and subsequent activation of inflammatory and immune system programs impairs anti-tumoral defense pathways. Moreover, we identify several markers of tumor development and progression previously unrelated to melanoma, and determined a prognostic signature with potential clinical utility.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Correlation of clinical and molecular markers
- Melanoma/skin cancers
- Molecular diagnosis and prognosis
- Molecular markers of metastasis and progression
- Tumor staging
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Wouters, Jasper
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Vizoso, Miguel
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Martinez-Cardus, ...
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Carmona, F Javie ...
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Govaere, Olivier
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Laguna, Teresa
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Joseph, Jesuchri ...
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Dynoodt, Peter
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Aura, Claudia
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Foth, Mona
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Cloots, Roy
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van den Hurk, Ka ...
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Balint, Balazs
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Murphy, Ian G.
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McDermott, Enda ...
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Sheahan, Kieran
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Jirström, Karin
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Nodin, Bjorn
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Mallya-Udupi, Gi ...
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Van den Oord, Jo ...
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Gallagher, Willi ...
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Esteller, Manel
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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BMC Medicine
- By the university
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Lund University