title: Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome.
abstract: We previously demonstrated that constitutional BUB1B mutations cause mosaic variegated aneuploidy, a condition characterized by constitutional aneuploidies and childhood cancer predisposition. To further investigate the role of BUB1B in cancer predisposition we performed comparative genomic hybridization analysis in an embryonal rhabdomyosarcoma from an MVA case with biallelic BUB1B mutations, revealing aneuploidies typical of sporadic E-RMS, with gain of chromosomes 3, 8, 13 and loss of chromosomes 9, 14, X. To investigate whether somatic BUB1B mutations occur in sporadic childhood cancers we screened 30 Wilms tumours, 10 acute lymphoblastic leukemias, nine rhabdomyosarcomas and 11 rhabdomyosarcoma cell lines for BUB1B mutations. We identified seven exonic and six intronic variants. Six of the exonic variants were synonymous and one resulted in a non-synonymous conservative missense alteration that was also present in a control. These data suggest that the genetic progression in rhabdomyosarcoma from MVA and non-MVA cases may be similar, but that somatic BUB1B mutations are unlikely to be common in sporadic childhood cancers known to be associated with MVA.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanks
authors.forename: Kim
authors.initials: K
authors.lastname: Coleman
authors.forename: Brenda
authors.initials: B
authors.lastname: Summersgill
authors.forename: Boo
authors.initials: B
authors.lastname: Messahel
authors.forename: Dan
authors.initials: D
authors.lastname: Williamson
authors.forename: Kathryn
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: Jon
authors.initials: J
authors.lastname: Strefford
authors.forename: John
authors.initials: J
authors.lastname: Swansbury
authors.forename: Alberto
authors.initials: A
authors.lastname: Plaja
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
mesh_terms: D000782:Aneuploidy; D002648:Child; D006801:Humans; D009030:Mosaicism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases
chemical_list: D011494:Protein Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases