title: Aberrant methylation patterns in colorectal cancer: a meta-analysis.
abstract: Colorectal cancer is among the leading causes of cancer death worldwide. Despite numerous molecular characterizations of the phenomenon, the exact dynamics of its onset and progression remain elusive. Colorectal cancer onset has been characterized by changes in DNA methylation profiles, that, owing to the stability of their patterns, are promising candidates to shed light on the molecular events laying at the base of this phenomenon.To exploit this stability and reinforce it, we conducted a meta-analysis on publicly available DNA methylation datasets generated on: normal colorectal, adenoma (ADE) and adenocarcinoma (CRC) samples using the Illumina 450k array, in the systems medicine frame, searching for tumor gene episignatures, to produce a carefully selected list of potential drivers, markers and targets of the disease. The analysis proceeds from a differential meta-analysis of the methylation profiles using an analytical pipeline recently developed by our group [1], through network reconstruction, topological and functional analyses, to finally highlight relevant epigenomic features. Our results show that genes already highlighted for their genetic or transcriptional alteration in colorectal cancer are also differentially methylated, reinforcing -regardless of the level of cellular control- their role in the complex of alterations involved in tumorigenesis.These findings were finally validated in an independent cohort from The Cancer Genome Atlas (TCGA).
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy.|National Counsel of Technological and Scientific Development (CNPq), ministry of science technology and innovation (MCTI), Brasilia, Brazil.
authors.forename: Danielle Fernandes
authors.initials: DF
authors.lastname: Durso
authors.affiliation: IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bacalini
authors.affiliation: CAPES Foundation, Ministry of Education of Brazil-Brasília (DF), Brazil.|Department of Physics and Astronomy, University of Bologna, Bologna, Italy.
authors.forename: Ítalo Faria
authors.initials: ÍF
authors.lastname: do Valle
authors.affiliation: IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pirazzini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonafé
authors.affiliation: Department of Physics and Astronomy, University of Bologna, Bologna, Italy.
authors.forename: Gastone
authors.initials: G
authors.lastname: Castellani
authors.affiliation: Biochemistry and Immunology Department, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Ana Maria Caetano
authors.initials: AM
authors.lastname: Faria
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy.|IRCCS Institute of Neurological Sciences, Bologna, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna, Italy.|Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
authors.affiliation: Personal Genomics S.r.l., Verona, Italy.
authors.forename: Christine
authors.initials: C
authors.lastname: Nardini
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D006801:Humans
keywords: DNA methylation; colorectal cancer; differential analysis; infinium human methylation 450; network analysis