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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2021
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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) |
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colon cancer consensus molecular subtypes marker panel methylation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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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 |
work_keys_str_mv |
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