Consensus molecular subtype classification of colorectal adenomas

Malgorzata A. Komor, Linda J. W. Bosch, Gergana Bounova, Anne S. Bolijn, Pien M. Delis-van Diemen, Christian Rausch, Youri Hoogstrate, Andrew P. Stubbs, Mark de Jong, Guido Jenster, Nicole C. T. van Grieken, Beatriz Carvalho, Lodewyk F. A. Wessels, Connie R. Jimenez, Remond J. A. Fijneman, Gerrit A. Meijer, In collaboration with the NGS-ProToCol Consortium:

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87%) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73%). One of the two adenomas showing MSI was classified as CMS1 (2%), the ‘MSI immune’ subtype. Eight adenomas (13%) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Original languageEnglish
Pages (from-to)266-276
JournalJournal of Pathology
Volume246
Issue number3
Early online date3 Jul 2018
DOIs
Publication statusPublished - 2018

Cite this

Komor, M. A., Bosch, L. J. W., Bounova, G., Bolijn, A. S., Delis-van Diemen, P. M., Rausch, C., ... In collaboration with the NGS-ProToCol Consortium: (2018). Consensus molecular subtype classification of colorectal adenomas. Journal of Pathology, 246(3), 266-276. https://doi.org/10.1002/path.5129
Komor, Malgorzata A. ; Bosch, Linda J. W. ; Bounova, Gergana ; Bolijn, Anne S. ; Delis-van Diemen, Pien M. ; Rausch, Christian ; Hoogstrate, Youri ; Stubbs, Andrew P. ; de Jong, Mark ; Jenster, Guido ; van Grieken, Nicole C. T. ; Carvalho, Beatriz ; Wessels, Lodewyk F. A. ; Jimenez, Connie R. ; Fijneman, Remond J. A. ; Meijer, Gerrit A. ; In collaboration with the NGS-ProToCol Consortium:. / Consensus molecular subtype classification of colorectal adenomas. In: Journal of Pathology. 2018 ; Vol. 246, No. 3. pp. 266-276.
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title = "Consensus molecular subtype classification of colorectal adenomas",
abstract = "Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87{\%}) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73{\%}). One of the two adenomas showing MSI was classified as CMS1 (2{\%}), the ‘MSI immune’ subtype. Eight adenomas (13{\%}) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC. {\circledC} 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.",
author = "Komor, {Malgorzata A.} and Bosch, {Linda J. W.} and Gergana Bounova and Bolijn, {Anne S.} and {Delis-van Diemen}, {Pien M.} and Christian Rausch and Youri Hoogstrate and Stubbs, {Andrew P.} and {de Jong}, Mark and Guido Jenster and {van Grieken}, {Nicole C. T.} and Beatriz Carvalho and Wessels, {Lodewyk F. A.} and Jimenez, {Connie R.} and Fijneman, {Remond J. A.} and Meijer, {Gerrit A.} and Natasja Dits and Rene Bottcher and Hiemstra, {Annemieke C.} and Bauke Ylstra and Daoud Sie and {van den Broek}, Evert and {van der Meer}, David and Floor Pepers and Eric Caldenhoven and Bart Janssen and {van Workum}, Wilbert and {van Lieshout}, Stef and Bangma, {Chris H.} and {van Leenders}, Geert and {van de Werken}, Harmen and Natasja Dits and Rene Bottcher and Hiemstra, {Annemieke C.} and Bauke Ylstra and Daoud Sie and {van den Broek}, Evert and {van der Meer}, David and Floor Pepers and Eric Caldenhoven and Bart Janssen and {van Workum}, Wilbert and {van Lieshout}, Stef and Bangma, {Chris H.} and {van Leenders}, Geert and {van de Werken}, Harmen and {In collaboration with the NGS-ProToCol Consortium:}",
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year = "2018",
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Komor, MA, Bosch, LJW, Bounova, G, Bolijn, AS, Delis-van Diemen, PM, Rausch, C, Hoogstrate, Y, Stubbs, AP, de Jong, M, Jenster, G, van Grieken, NCT, Carvalho, B, Wessels, LFA, Jimenez, CR, Fijneman, RJA, Meijer, GA & In collaboration with the NGS-ProToCol Consortium: 2018, 'Consensus molecular subtype classification of colorectal adenomas' Journal of Pathology, vol. 246, no. 3, pp. 266-276. https://doi.org/10.1002/path.5129

Consensus molecular subtype classification of colorectal adenomas. / Komor, Malgorzata A.; Bosch, Linda J. W.; Bounova, Gergana; Bolijn, Anne S.; Delis-van Diemen, Pien M.; Rausch, Christian; Hoogstrate, Youri; Stubbs, Andrew P.; de Jong, Mark; Jenster, Guido; van Grieken, Nicole C. T.; Carvalho, Beatriz; Wessels, Lodewyk F. A.; Jimenez, Connie R.; Fijneman, Remond J. A.; Meijer, Gerrit A.; In collaboration with the NGS-ProToCol Consortium:.

In: Journal of Pathology, Vol. 246, No. 3, 2018, p. 266-276.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Consensus molecular subtype classification of colorectal adenomas

AU - Komor, Malgorzata A.

AU - Bosch, Linda J. W.

AU - Bounova, Gergana

AU - Bolijn, Anne S.

AU - Delis-van Diemen, Pien M.

AU - Rausch, Christian

AU - Hoogstrate, Youri

AU - Stubbs, Andrew P.

AU - de Jong, Mark

AU - Jenster, Guido

AU - van Grieken, Nicole C. T.

AU - Carvalho, Beatriz

AU - Wessels, Lodewyk F. A.

AU - Jimenez, Connie R.

AU - Fijneman, Remond J. A.

AU - Meijer, Gerrit A.

AU - Dits, Natasja

AU - Bottcher, Rene

AU - Hiemstra, Annemieke C.

AU - Ylstra, Bauke

AU - Sie, Daoud

AU - van den Broek, Evert

AU - van der Meer, David

AU - Pepers, Floor

AU - Caldenhoven, Eric

AU - Janssen, Bart

AU - van Workum, Wilbert

AU - van Lieshout, Stef

AU - Bangma, Chris H.

AU - van Leenders, Geert

AU - van de Werken, Harmen

AU - Dits, Natasja

AU - Bottcher, Rene

AU - Hiemstra, Annemieke C.

AU - Ylstra, Bauke

AU - Sie, Daoud

AU - van den Broek, Evert

AU - van der Meer, David

AU - Pepers, Floor

AU - Caldenhoven, Eric

AU - Janssen, Bart

AU - van Workum, Wilbert

AU - van Lieshout, Stef

AU - Bangma, Chris H.

AU - van Leenders, Geert

AU - van de Werken, Harmen

AU - In collaboration with the NGS-ProToCol Consortium:

N1 - This article is protected by copyright. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87%) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73%). One of the two adenomas showing MSI was classified as CMS1 (2%), the ‘MSI immune’ subtype. Eight adenomas (13%) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

AB - Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87%) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73%). One of the two adenomas showing MSI was classified as CMS1 (2%), the ‘MSI immune’ subtype. Eight adenomas (13%) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/29968252

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