TY - JOUR
T1 - Consensus molecular subtype classification of colorectal adenomas
AU - In collaboration with the NGS-ProToCol Consortium:
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
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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052805979&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29968252
U2 - https://doi.org/10.1002/path.5129
DO - https://doi.org/10.1002/path.5129
M3 - Article
C2 - 29968252
SN - 0022-3417
VL - 246
SP - 266
EP - 276
JO - Journal of pathology
JF - Journal of pathology
IS - 3
ER -