Gene methylation in rectal cancer: Predictive marker of response to chemoradiotherapy?

Chiara Molinari, Valentina Casadio, Flavia Foca, Chiara Zingaretti, Massimo Giannini, Andrea Avanzolini, Enrico Lucci, Luca Saragoni, Alessandro Passardi, Dino Amadori, Daniele Calistri, Wainer Zoli

Research output: Contribution to journalArticlepeer-review

Abstract

Although numerous studies have focused on the link between CpG island methylator phenotypes and the development of colorectal cancer, few studies have dealt specifically with methylation profiling in rectal cancer and its role in predicting response to neoadjuvant chemoradiotherapy (NCRT). We characterized methylation profiles in normal and neoplastic tissue samples from patients with rectal cancer and assessed the role of this molecular profile in predicting chemoradioactivity. We evaluated 74 pretreatment tumor samples and 16 apparently normal tissue biopsies from rectal cancer patients submitted to NCRT. The methylation profile of 24 different tumor suppressor genes was analyzed from FFPE samples by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Methylation status was studied in relation to tissue type and clinical pathological parameters, in particular, pathological response evaluated by tumor regression grade (TRG). ESR1, CDH13, RARB, IGSF4, and APC genes showed high methylation levels in tumor samples (range 18.92-49.77) with respect to normal tissue. Methylation levels of the remaining genes were low and similar in both normal (range 1.91-14.56) and tumor tissue (range 1.84-11). Analysis of the association between methylation and response to therapy in tumor samples showed that only TIMP3 methylation status differed significantly within the four TRG classes (ANOVA, P

Original languageEnglish
Pages (from-to)2343-2349
Number of pages7
JournalJournal of Cellular Physiology
Volume228
Issue number12
DOIs
Publication statusPublished - Dec 2013

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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