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Title: Multiple sporadic colorectal cancers display a unique methylation phenotype.
Author: Gonzalo, Victoria
Lozano Salvatella, Juan José
Alonso-Espinaco, Virginia
Moreira, Leticia
Muñoz, Jenifer
Pellisé Urquiza, Maria
Castellví Bel, Sergi
Bessa i Caserras, Xavier
Andreu, Montserrat
Xicola, Rosa
Llor, Xavier
Ruiz-Ponte, Clara
Carracedo Álvarez, Ángel
Jover, Rodrigo
Castells Garangou, Antoni
Balaguer Prunés, Francesc
Keywords: Càncer colorectal
Mutació (Biologia)
Colorectal cancer
Mutation (Biology)
Issue Date: 18-Mar-2014
Publisher: Public Library of Science (PLoS)
Abstract: Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity.
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It is part of: PLoS One, 2014, vol. 9, num. 3, p. e91033
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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