Research Papers:
Aberrant methylation patterns in colorectal cancer: a meta-analysis
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Abstract
Danielle Fernandes Durso1,2,*, Maria Giulia Bacalini3,*, Ítalo Faria do Valle4,5, Chiara Pirazzini3, Massimiliano Bonafé1, Gastone Castellani5, Ana Maria Caetano Faria6, Claudio Franceschi1,3,7,*, Paolo Garagnani1,7,8,*, Christine Nardini9,*
1Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy
2National Counsel of Technological and Scientific Development (CNPq), ministry of science technology and innovation (MCTI), Brasilia, Brazil
3IRCCS Institute of Neurological Sciences, Bologna, Italy
4CAPES Foundation, Ministry of Education of Brazil–Brasília (DF), Brazil
5Department of Physics and Astronomy, University of Bologna, Bologna, Italy
6Biochemistry and Immunology Department, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil
7Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
8Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna, Italy
9Personal Genomics S.r.l., Verona, Italy
*These authors contributed equally to this work
Correspondence to:
Christine Nardini, email: [email protected]
Paolo Garagnani, email: [email protected]
Claudio Franceschi, email: [email protected]
Keywords: DNA methylation, colorectal cancer, differential analysis, network analysis, infinium human methylation 450
Received: June 08, 2016 Accepted: December 27, 2016 Published: January 10, 2017
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).
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