A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer

Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). We aim to identify methylation markers to distinguish between CMS2 and CMS3 in patients with CRC, for which an easy test is currently lacking. To this aim, fresh‐frozen tumor tissue of 239 patients with sta...

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Autores principales: Inge van denBerg, Marcel Smid, Robert R. J. Coebergh van den Braak, Mark A. van deWiel, Carolien H. M. vanDeurzen, Vanja deWeerd, John W. M. Martens, Jan N. M. IJzermans, Saskia M. Wilting
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Publicado: Wiley 2021
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Acceso en línea:https://doaj.org/article/00cc8da0246e4a18907d6f294fb0eba1
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spelling oai:doaj.org-article:00cc8da0246e4a18907d6f294fb0eba12021-12-02T10:31:06ZA panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer1878-02611574-789110.1002/1878-0261.13098https://doaj.org/article/00cc8da0246e4a18907d6f294fb0eba12021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13098https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). We aim to identify methylation markers to distinguish between CMS2 and CMS3 in patients with CRC, for which an easy test is currently lacking. To this aim, fresh‐frozen tumor tissue of 239 patients with stage I‐III CRC was analyzed. Methylation profiles were obtained using the Infinium HumanMethylation450 BeadChip. We performed adaptive group‐regularized logistic ridge regression with post hoc group‐weighted elastic net marker selection to build prediction models for classification of CMS2 and CMS3. The Cancer Genome Atlas (TCGA) data were used for validation. Group regularization of the probes was done based on their location either relative to a CpG island or relative to a gene present in the CMS classifier, resulting in two different prediction models and subsequently different marker panels. For both panels, even when using only five markers, accuracies were > 90% in our cohort and in the TCGA validation set. Our methylation marker panel accurately distinguishes between CMS2 and CMS3. This enables development of a targeted assay to provide a robust and clinically relevant classification tool for CRC patients.Inge van denBergMarcel SmidRobert R. J. Coebergh van den BraakMark A. van deWielCarolien H. M. vanDeurzenVanja deWeerdJohn W. M. MartensJan N. M. IJzermansSaskia M. WiltingWileyarticlecolon cancerconsensus molecular subtypesmarker panelmethylationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3348-3362 (2021)
institution DOAJ
collection DOAJ
language EN
topic colon cancer
consensus molecular subtypes
marker panel
methylation
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle colon cancer
consensus molecular subtypes
marker panel
methylation
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Inge van denBerg
Marcel Smid
Robert R. J. Coebergh van den Braak
Mark A. van deWiel
Carolien H. M. vanDeurzen
Vanja deWeerd
John W. M. Martens
Jan N. M. IJzermans
Saskia M. Wilting
A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
description Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). We aim to identify methylation markers to distinguish between CMS2 and CMS3 in patients with CRC, for which an easy test is currently lacking. To this aim, fresh‐frozen tumor tissue of 239 patients with stage I‐III CRC was analyzed. Methylation profiles were obtained using the Infinium HumanMethylation450 BeadChip. We performed adaptive group‐regularized logistic ridge regression with post hoc group‐weighted elastic net marker selection to build prediction models for classification of CMS2 and CMS3. The Cancer Genome Atlas (TCGA) data were used for validation. Group regularization of the probes was done based on their location either relative to a CpG island or relative to a gene present in the CMS classifier, resulting in two different prediction models and subsequently different marker panels. For both panels, even when using only five markers, accuracies were > 90% in our cohort and in the TCGA validation set. Our methylation marker panel accurately distinguishes between CMS2 and CMS3. This enables development of a targeted assay to provide a robust and clinically relevant classification tool for CRC patients.
format article
author Inge van denBerg
Marcel Smid
Robert R. J. Coebergh van den Braak
Mark A. van deWiel
Carolien H. M. vanDeurzen
Vanja deWeerd
John W. M. Martens
Jan N. M. IJzermans
Saskia M. Wilting
author_facet Inge van denBerg
Marcel Smid
Robert R. J. Coebergh van den Braak
Mark A. van deWiel
Carolien H. M. vanDeurzen
Vanja deWeerd
John W. M. Martens
Jan N. M. IJzermans
Saskia M. Wilting
author_sort Inge van denBerg
title A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
title_short A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
title_full A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
title_fullStr A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
title_full_unstemmed A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
title_sort panel of dna methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
publisher Wiley
publishDate 2021
url https://doaj.org/article/00cc8da0246e4a18907d6f294fb0eba1
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