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However, as only a minority of adenomas progress to cancer, such strategies may lead to overtreatment. The present study aimed to characterize adenomas by in\u2010depth molecular profiling, to obtain insights into altered biology associated with the colorectal adenoma\u2010to\u2010carcinoma progression. We obtained low\u2010coverage whole genome sequencing, RNA sequencing and tandem mass spectrometry data for 30 CRCs, 30 adenomas and 18 normal adjacent colon samples. These data were used for DNA copy number aberrations profiling, differential expression, gene set enrichment and gene\u2010dosage effect analysis. Protein expression was independently validated by immunohistochemistry on tissue microarrays and in patient\u2010derived colorectal adenoma organoids. Stroma percentage was determined by digital image analysis of tissue sections. Twenty\u2010four out of 30 adenomas could be unambiguously classified as high risk (<jats:italic>n<\/jats:italic> =\u20099) or low risk (<jats:italic>n<\/jats:italic> =\u200915) of progressing to cancer, based on DNA copy number profiles. Biological processes more prevalent in high\u2010risk than low\u2010risk adenomas were related to proliferation, tumor microenvironment and Notch, Wnt, PI3K\/AKT\/mTOR and Hedgehog signaling, while metabolic processes and protein secretion were enriched in low\u2010risk adenomas. DNA copy number driven gene\u2010dosage effect in high\u2010risk adenomas and cancers was observed for <jats:italic>POFUT1<\/jats:italic>, <jats:italic>RPRD1B<\/jats:italic> and <jats:italic>EIF6<\/jats:italic>. Increased POFUT1 expression in high\u2010risk adenomas was validated in tissue samples and organoids. High POFUT1 expression was also associated with Notch signaling enrichment and with decreased goblet cells differentiation. In\u2010depth molecular characterization of colorectal adenomas revealed <jats:italic>POFUT1<\/jats:italic> and Notch signaling as potential drivers of tumor progression.<\/jats:p>","DOI":"10.1002\/ijc.32627","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T16:00:21Z","timestamp":1565798421000},"page":"1979-1992","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Molecular characterization of colorectal adenomas reveals POFUT1 as a candidate driver of tumor progression"],"prefix":"10.1002","volume":"146","author":[{"given":"Malgorzata A.","family":"Komor","sequence":"first","affiliation":[{"name":"Department of Pathology Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Oncoproteomics Laboratory, Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology  Amsterdam The 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