Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/114168
Title: Epigenetic homogeneity within colorectal tumors predicts shorter relapse-free and overall survival times for patients with locoregional cancer
Author: Martínez-Cardús, Anna
Moran, Sebastian
Musulen, Eva
Moutinho, Cátia
Manzano, Jose Luis
Martínez-Balibrea, Eva
Tierno, Montserrat
Élez, Elena
Landolfi, Stefania
Lorden, Patricia
Arribas, Carles
Müller, Fabian
Bock, Christoph
Esteller, Manel
Keywords: Epigènesi
Marcadors bioquímics
ADN
Metilació
Càncer colorectal
Malalts de càncer
Epigenesis
Biochemical markers
DNA
Methylation
Colorectal cancer
Cancer patients
Issue Date: Nov-2016
Publisher: Elsevier
Abstract: Background & aims: there are few validated biomarkers that can be used to predict outcomes for patients with colorectal cancer. Part of the challenge is the genetic and molecular heterogeneity of colorectal tumors not only among patients, but also within tumors. We have explored intratumor heterogeneity at the epigenetic level, due to its dynamic nature. We analyzed DNA methylation profiles of the digestive tract surface and the central bulk and invasive front regions of colorectal tumors. Methods: we determined the DNA methylation profiles of >450,000 CpG sites in 3 macrodissected regions of 79 colorectal tumors and 23 associated liver metastases, obtained from 2 hospitals in Spain. We also analyzed samples for KRAS and BRAF mutations, 499,170 single nucleotide polymorphisms, and performed immunohistochemical analyses. Results: we observed differences in DNA methylation among the 3 tumor sections; regions of tumor−host interface differed the most from the other tumor sections. Interestingly, tumor samples collected from areas closer to the gastrointestinal transit most frequently shared methylation events with metastases. When we calculated individual coefficients to quantify heterogeneity, we found that epigenetic homogeneity was significantly associated with short time of relapse-free survival (log-rank P = .037) and short time of overall survival (log-rank P = .026) in patients with locoregional colorectal cancer. Conclusions: in an analysis of 79 colorectal tumors, we found significant heterogeneity in patterns of DNA methylation within each tumor; the level of heterogeneity correlates with times of relapse-free and overall survival.
Note: Reproducció del document publicat a: https://doi.org/10.1053/j.gastro.2016.08.001
It is part of: Gastroenterology, 2016, vol. 151, num. 5, p. 961-972
Related resource: https://doi.org/10.1053/j.gastro.2016.08.001
URI: http://hdl.handle.net/2445/114168
ISSN: 0016-5085
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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