title: Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours.
abstract: Wilms' tumour is one of the most common solid tumours of childhood. 11p13 (WT1 locus) and 11p15.5 (WT2 locus) are known to have genetic or epigenetic aberrations in these tumours. In Wilms' tumours, mutation of the Wilms tumour 1 (WT1) gene at the WT1 locus has been reported, and the WT2 locus, comprising the two independent imprinted domains IGF2/H19 and KIP2/LIT1, can undergo maternal deletion or alterations associated with imprinting. Although these alterations have been identified in many studies, it is still not clear how frequently combined genetic and epigenetic alterations of these loci are involved in Wilms' tumours or how these alterations occur. To answer both questions, we performed genetic and epigenetic analyses of these loci, together with an additional gene, CTNNB1, in 35 sporadic Wilms' tumours. Loss of heterozygosity of 11p15.5 and loss of imprinting of IGF2 were the most frequent genetic (29%) and epigenetic (40%) alterations in Wilms' tumours, respectively. In total, 83% of the tumours had at least one alteration at 11p15.5 and/or 11p13. One-third of the tumours had alterations at multiple loci. Our results suggest that chromosome 11p is not only genetically but also epigenetically critical for the majority of Wilms' tumours.
authors.affiliation: Division of Molecular Biology and Genetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Satoh
authors.forename: H
authors.initials: H
authors.lastname: Nakadate
authors.forename: T
authors.initials: T
authors.lastname: Nakagawachi
authors.forename: K
authors.initials: K
authors.lastname: Higashimoto
authors.forename: K
authors.initials: K
authors.lastname: Joh
authors.forename: Z
authors.initials: Z
authors.lastname: Masaki
authors.forename: J
authors.initials: J
authors.lastname: Uozumi
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Mukai
authors.forename: H
authors.initials: H
authors.lastname: Soejima
mesh_terms: D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics; D044127:Epigenesis, Genetic; D016162:Genes, Wilms Tumor; D006801:Humans; D007335:Insulin-Like Growth Factor II; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation; D011506:Proteins / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
chemical_list: C493964:CDKN1C protein, human; C495270:CTNNB1 protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C035170:IGF2 protein, human; D011506:Proteins; D051176:beta Catenin; D007335:Insulin-Like Growth Factor II