title: Association of 11q loss, trisomy 12, and possible 16q loss with loss of imprinting of insulin-like growth factor-II in Wilms tumor.
abstract: We evaluated the WT1 and IGF2 status and performed chromosome and/or comparative genomic hybridization analysis in 43 tumor samples from patients with Wilms tumor. On this basis, we classified them into 4 groups: WT1 abnormality, loss of heterozygosity (LOH) of IGF2, loss of imprinting (LOI) of IGF2, and retention of imprinting (ROI) of IGF2, which were seen in 12%, 30%, 16%, and 42% of the tumors, respectively. Patients in the LOI group were older than those in other groups (P < 0.01), and tumors in the WT1 group had fewer cytogenetic changes than did those in the other groups (P < 0.01). It was found that 11q- and +12 were more frequent in the LOI group than in the WT1+LOH+ROI group (P < 0.01 and P < 0.01). There was no difference in the incidence of 16q- between the LOI group and the other groups; however, when we excluded 16 tumors with LOH on 11p15, 16q- tended to be more frequent in the LOI group than in the WT1+ROI group (P = 0.06). The association of 11q- or +12 with LOI of IGF2 found in the present study suggests that many tumors with no WT1 abnormalities need overexpression of IGF2 together with biallelic inactivation of the tumor-suppressor gene on 11q and/or overexpression of growth-promoting genes on chromosome 12. The 11q gene may code for one of the proteins that constitute a CTCF insulator complex, and its mutation, deletion, or haploinsufficiency may cause insulator abnormalities that might lead to LOI of IGF2.
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Hisaya
authors.initials: H
authors.lastname: Nakadate
authors.forename: Masayuki
authors.initials: M
authors.lastname: Haruta
authors.forename: Waka
authors.initials: W
authors.lastname: Sugawara
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sasaki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kikuta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hata
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kaneko
mesh_terms: D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002885:Chromosomes, Human, Pair 16; D044127:Epigenesis, Genetic; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D019656:Loss of Heterozygosity; D009693:Nucleic Acid Hybridization; D014314:Trisomy; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
chemical_list: D025721:WT1 Proteins; D007335:Insulin-Like Growth Factor II