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Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development
Author(s) -
Weren Robbert DA,
Venkatachalam Ramprasath,
Cazier JeanBaptiste,
Farin Henner F,
Kets C Marleen,
de Voer Richarda M,
Vreede Lilian,
Verwiel Eugène TP,
van Asseldonk Monique,
Kamping Eveline J,
Kiemeney Lambertus A,
Neveling Kornelia,
Aben Katja KH,
CarvajalCarmona Luis,
Nagtegaal Iris D,
Schackert Hans K,
Clevers Hans,
van de Wetering Marc,
Tomlinson Ian P,
Ligtenberg Marjolijn JL,
Hoogerbrugge Nicoline,
Geurts van Kessel Ad,
Kuiper Roland P
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4520
Subject(s) - colorectal cancer , germline , bap1 , biology , cancer research , gene , germline mutation , cancer , genetics , mutation
Heritable genetic variants can significantly affect the lifetime risk of developing cancer, including polyposis and colorectal cancer ( CRC ). Variants in genes currently known to be associated with a high risk for polyposis or CRC , however, explain only a limited number of hereditary cases. The identification of additional genetic causes is, therefore, crucial to improve CRC prevention, detection and treatment. We have performed genome‐wide and targeted DNA copy number profiling and resequencing in early‐onset and familial polyposis/ CRC patients, and show that deletions affecting the open reading frame of the tumour suppressor gene FOCAD are recurrent and significantly enriched in CRC patients compared with unaffected controls. All patients carrying FOCAD deletions exhibited a personal or family history of polyposis. RNA in situ hybridization revealed FOCAD 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 FOCAD underlie moderate genetic predisposition to the development of polyposis and CRC . © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.