Association of 11q loss, trisomy 12, and possible 16q loss with loss of imprinting of insulin-like growth factor-II in Wilms tumor

Genes Chromosomes Cancer. 2006 Jun;45(6):592-601. doi: 10.1002/gcc.20321.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 16
  • Epigenesis, Genetic
  • Genomic Imprinting*
  • Humans
  • Infant
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Loss of Heterozygosity
  • Nucleic Acid Hybridization
  • Trisomy*
  • Tumor Cells, Cultured
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism
  • Wilms Tumor / genetics*
  • Wilms Tumor / metabolism


  • WT1 Proteins
  • Insulin-Like Growth Factor II