Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome

详细信息    查看全文

• 作者：Sandra Hanks ; Kim Coleman ; Brenda Summersgill ; Boo Messahel ; Dan Williamson ; Kathryn Pritchard-Jones ; Jon Strefford ; John Swansbury ; Alberto Plaja ; Janet Shipley and Nazneen Rahman
• 关键词：BUB1B ; Rhabdomyosarcoma ; Wilms tumour ; Aneuploidy ; Mosaic variegated aneuploidy
• 刊名：Cancer Letters
• 出版年：2006
• 出版时间：8 August 2006
• 年：2006
• 卷：239
• 期：2
• 页码：234-238
• 全文大小：85 K

文摘

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.