Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma

Autor: Olivier Govaere, Teresa Laguna, Mona Foth, F. Javier Carmona, Karin Jirström, Balázs Bálint, Kieran Sheahan, Manel Esteller, William M. Gallagher, Joost van den Oord, Girish Mallya-Udupi, Anna Martínez-Cardús, Roy Cloots, Claudia Aura, Jasper Wouters, Jesuchristopher Joseph, Ian G. Murphy, Peter Dynoodt, Karin van den Hurk, Björn Nodin, Miguel Vizoso, Enda W. McDermott
Přispěvatelé: Promovendi NTM, RS: GROW - R2 - Basic and Translational Cancer Biology, Universitat de Barcelona
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Skin Neoplasms
ADN
lcsh:Medicine
Bioinformatics
UP-REGULATION
MALIGNANT-MELANOMA
EXPRESSION PROFILES
Melanoma/skin cancers
0302 clinical medicine
Skin cancer
PROMOTER METHYLATION
METASTATIC MELANOMA
TUMOR PROGRESSION
Melanoma
Epigenomics
Aged
80 and over
Molecular markers of metastasis and progression
General Medicine
DNA
Neoplasm
Middle Aged
Prognosis
3. Good health
GENOME
030220 oncology & carcinogenesis
Tumor markers
DNA methylation
Disease Progression
Immunohistochemistry
Epigenetics
Female
Metilació
Research Article
Adult
CELL-LINES
Molecular diagnosis and prognosis
Methylation
03 medical and health sciences
Breast cancer
medicine
Biomarkers
Tumor
Humans
BREAST-CANCER
Càncer de pell
Aged
POLYMERASE-1
business.industry
Marcadors tumorals
lcsh:R
DNA
DNA Methylation
Tumor staging
medicine.disease
Epigenètica
Correlation of clinical and molecular markers
030104 developmental biology
Tumor progression
Cutaneous melanoma
Cancer research
business
Zdroj: BMC Medicine, Vol 15, Iss 1, Pp 1-16 (2017)
BMC Medicine, 15:101. BioMed Central Ltd
BMC Medicine
Dipòsit Digital de la UB
Universidad de Barcelona
Recercat. Dipósit de la Recerca de Catalunya
instname
ISSN: 1741-7015
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0851-3) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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