title: Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are risk factors for colorectal cancer.
abstract: The spindle assembly checkpoint controls proper chromosome segregation during mitosis and prevents aneuploidy-an important feature of cancer cells. We performed genome-wide and targeted copy number and mutation analyses of germline DNA from 208 patients with familial or early-onset (40 years of age or younger) colorectal cancer; we identified haploinsufficiency or heterozygous mutations in the spindle assembly checkpoint genes BUB1 and BUB3 in 2.9% of them. Besides colorectal cancer, these patients had variegated aneuploidies in multiple tissues and variable dysmorphic features. These results indicate that mutations in BUB1 and BUB3 cause mosaic variegated aneuploidy and increase the risk of colorectal cancer at a young age.
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre and Research Institute for Oncology, Nijmegen, The Netherlands.
authors.forename: Richarda M
authors.initials: RM
authors.lastname: de Voer
authors.forename: Ad
authors.initials: A
authors.lastname: Geurts van Kessel
authors.forename: Robbert D A
authors.initials: RD
authors.lastname: Weren
authors.forename: Marjolijn J L
authors.initials: MJ
authors.lastname: Ligtenberg
authors.forename: Dominique
authors.initials: D
authors.lastname: Smeets
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
authors.forename: Lilian
authors.initials: L
authors.lastname: Vreede
authors.forename: Eveline J
authors.initials: EJ
authors.lastname: Kamping
authors.forename: Eugène T P
authors.initials: ET
authors.lastname: Verwiel
authors.forename: Marc-Manuel
authors.initials: MM
authors.lastname: Hahn
authors.forename: Maayke
authors.initials: M
authors.lastname: Ariaans
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Spruijt
authors.forename: Ton
authors.initials: T
authors.lastname: van Essen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houge
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Sheng
authors.forename: Hanka
authors.initials: H
authors.lastname: Venselaar
authors.forename: Conny M A
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
authors.forename: J Han J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Nicoline
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: Roland P
authors.initials: RP
authors.lastname: Kuiper
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D055106:Genome-Wide Association Study; D018095:Germ-Line Mutation; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: C489444:BUB3 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: CRC; Cancer Predisposition; MVA; Mosaic Variegated Aneuploidy; SAC; Spindle Assembly Checkpoint; colorectal cancer; mosaic variegated aneuploidy; spindle assembly checkpoint