Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B.
Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.
Hanks
Sandra
S
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Coleman
Kim
K
Reid
Sarah
S
Plaja
Alberto
A
Firth
Helen
H
Fitzpatrick
David
D
Kidd
Alexa
A
Méhes
Károly
K
Nash
Richard
R
Robin
Nathanial
N
Shannon
Nora
N
Tolmie
John
J
Swansbury
John
J
Irrthum
Alexandre
A
Douglas
Jenny
J
Rahman
Nazneen
N
D000015:Abnormalities, Multiple / Q000235:genetics*; D000483:Alleles; D000782:Aneuploidy; D018797:Cell Cycle Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D008941:Spindle Apparatus
D018797:Cell Cycle Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases