University of Oulu

Turpín-Sevilla, M.d.C.; Pérez-Sanz, F.; García-Solano, J.; Sebastián-León, P.; Trujillo-Santos, J.; Carbonell, P.; Estrada, E.; Tuomisto, A.; Herruzo, I.; Fennell, L.J.; Mäkinen, M.J.; Rodríguez-Braun, E.; Whitehall, V.L.J.; Conesa, A.; Conesa-Zamora, P. Global Methylome Scores Correlate with Histological Subtypes of Colorectal Carcinoma and Show Different Associations with Common Clinical and Molecular Features. Cancers 2021, 13, 5165.

Global methylome scores correlate with histological subtypes of colorectal carcinoma and show different associations with common clinical and molecular features

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Author: Turpín-Sevilla, María del Carmen1; Pérez-Sanz, Fernando2; García-Solano, José3,4,5;
Organizations: 1Facultad de Medicina, Universidad Francisco de Vitoria, Ctra. Pozuelo-Majadahonda, Km 1800, Pozuelo de Alarcón, 28223 Madrid, Spain
2Biomedical Informatics & Bioinformatics Platform, Institute for Biomedical Research of Murcia (IMIB)/Foundation for Healthcare Training & Research of the Region of Murcia (FFIS), Calle Luis Fontes Pagán 9, 30003 Murcia, Spain
3Department of Pathology, Santa Lucía General University Hospital (HGUSL), C/Mezquita s/n, 30202 Cartagena, Spain
4Facultad de Ciencias de la Salud, Universidad Católica de Murcia (UCAM), Campus Los Jerónimos, 30107 Guadalupe, Spain
5Group of Molecular Pathology and Pharmacogenetics, Institute for Biomedical Research from Murcia (IMIB), HGUSL, 30202 Cartagena, Spain
6IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
7Department of Internal Medicine, Santa Lucía General University Hospital (HGUSL), C/Mezquita s/n, 30202 Cartagena, Spain
8Biochemistry and Clinical Genetic Center, Virgen de la Arrixaca University Hospital, 30100 Murcia, Spain
9Department of Social Psychology and Methodology, Universidad Autónoma de Madrid, 28049 Madrid, Spain
10Cancer and Translational Medicine Research Unit, Department of Pathology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland
11QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
12Conjoint Internal Medicine Laboratory, Pathology Queensland, Herston, QLD 4006, Australia
13Faculty of Medicine, The University of Queensland, Herston, QLD 4072, Australia
14Clinical Oncology Department, Santa Lucía General University Hospital (HGUSL). C/Mezquita s/n, 30202 Cartagena, Spain
15Microbiology and Cell Sciences Department, Institute for Food and Agricultural Sciences, Genetics Institute, University of Florida, Gainesville, FL 32611, USA
16Department of Clinical Analysis, Santa Lucía General University Hospital (HGUSL), C/Mezquita s/n, 30202 Cartagena, Spain
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-11-18


Background: The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina’s 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI-H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied.

Results: SAC has an intermediate methylation pattern between CC and hmMSI-H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores).

Conclusion: These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs.

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Series: Cancers
ISSN: 2072-6694
ISSN-E: 2072-6694
ISSN-L: 2072-6694
Volume: 13
Issue: 20
Article number: 5165
DOI: 10.3390/cancers13205165
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by two grants from Instituto de Salud Carlos III, Ministerio de Sanidad, Spain and FEDER funds (refs: PI12-1232, PI18-0144) and another from the European Union’s Horizon 2020 research and innovation program (ref. 848098).
Copyright information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (