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).

Aberrant methylation patterns in colorectal cancer: A meta-analysis

Durso, Danielle Fernandes;BACALINI, MARIA GIULIA;PIRAZZINI, CHIARA;BONAFE', MASSIMILIANO;CASTELLANI, GASTONE;FRANCESCHI, CLAUDIO;GARAGNANI, PAOLO;
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).
Durso, Danielle Fernandes; Bacalini, Maria Giulia; do Valle, Ítalo Faria; Pirazzini, Chiara; Bonafé, Massimiliano; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine
File in questo prodotto:
File Dimensione Formato  
Aberrant methylation patterns in colorectal cancer a meta-analysis.pdf

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale - Condividi allo stesso modo (CCBYNCSA)
Dimensione 2.2 MB
Formato Adobe PDF
2.2 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/580718
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact