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Variants in genes currently known to be associated with a high risk for polyposis or <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content>, however, explain only a limited number of hereditary cases. The identification of additional genetic causes is, therefore, crucial to improve <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content> prevention, detection and treatment. We have performed genome\u2010wide and targeted <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> copy number profiling and resequencing in early\u2010onset and familial polyposis\/<jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content> patients, and show that deletions affecting the open reading frame of the tumour suppressor gene <jats:italic><jats:styled-content style=\"fixed-case\">FOCAD<\/jats:styled-content><\/jats:italic> are recurrent and significantly enriched in <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content> patients compared with unaffected controls. All patients carrying <jats:italic><jats:styled-content style=\"fixed-case\">FOCAD<\/jats:styled-content><\/jats:italic> deletions exhibited a personal or family history of polyposis. <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> <jats:italic>in situ<\/jats:italic> hybridization revealed <jats:italic><jats:styled-content style=\"fixed-case\">FOCAD<\/jats:styled-content><\/jats:italic> expression in epithelial cells in the colonic crypt, the site of tumour initiation, as well as in colonic tumours and organoids. Our data suggest that monoallelic germline deletions in the tumour suppressor gene <jats:italic><jats:styled-content style=\"fixed-case\">FOCAD<\/jats:styled-content><\/jats:italic> underlie moderate genetic predisposition to the development of polyposis and <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content>. \u00a9 2015 Authors. Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.4520","type":"journal-article","created":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T01:24:48Z","timestamp":1424827488000},"page":"155-164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Germline deletions in the tumour suppressor gene <i><scp>FOCAD<\/scp><\/i> are associated with polyposis and colorectal cancer development"],"prefix":"10.1002","volume":"236","author":[{"given":"Robbert DA","family":"Weren","sequence":"first","affiliation":[{"name":"Department of Human Genetics Radboud university medical center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramprasath","family":"Venkatachalam","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud university medical center  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