Abstract 3676: CMS classification of colorectal adenomas

Background Consensus molecular subtyping (CMS) is an RNA-expression-based classification of colorectal cancers (CRC). Genomic alterations, resulting in specific RNA-expression patterns, accumulate during CRC pathogenesis, including the premalignant adenoma stage. Aim This study aimed to investigate whether differentiation of colorectal neoplasia into CMS classes can already be recognized at the adenoma stage, and whether specific CMS classes could be associated with DNA copy number aberrations that mark adenomas at high-risk of progressing to CRC. Materials and Methods RNA-sequencing was performed on 62 advanced adenomas and 59 CRCs. DNA copy number analysis in adenomas was performed by low-coverage DNA-sequencing (n=30) or array-Comparative Genomic Hybridization (n=32). Microsatellite instability (MSI) status was determined by PCR methods. Adenomas and CRCs were classified into CMS subtypes together with CRCs (n=556) from The Cancer Genome Atlas, using the Random Forest CMS classifier. Results The majority of the adenomas were classified as CMS3 (n=45; 72%), the 9metabolic subtype9, recognized as least common among CRCs. No adenomas were classified as the 9mesenchymal9 CMS4 subtype. One adenoma was classified as the 9MSI immune9 CMS1 (2%), and 8 adenomas as the 9canonical9 CMS2 (13%) type. The remaining 8 (13%) could not be classified. The CMS3 class was enriched with adenomas at low-risk of progression. Conclusion Most adenomas were successfully classified. The lack of CMS4 adenomas is consistent with the fact that adenomas lack invasion-associated stroma. Adenomas showing cancer-associated chromosomal instability (CIN) or MSI (24%) were mostly classified as CMS2 and CMS1, respectively. The CMS3 subtype appeared to be the predominant adenoma signature. Citation Format: Malgorzata A. Komor, Linda J. Bosch, Gergana Bounova, Anne S. Bolijn, Pien Delis-van Diemen, Christian Rausch, Youri Hoogstrate, Andrew Stubbs, Mark de Jong, Guido Jenster, Nicole C. an Grieken, Beatriz Carvalho, Lodewyk Wessels, Connie R. Jimenez, Remond J. Fijneman, Gerrit A. Meijer, NGS-ProToCol Consortium. CMS classification of colorectal adenomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3676.