title: A high incidence of WT1 abnormality in bilateral Wilms tumours in Japan, and the penetrance rates in children with WT1 germline mutation.
abstract: BACKGROUND
  Bilateral Wilms tumours (BWTs) occur by germline mutation of various predisposing genes; one of which is WT1 whose abnormality was reported in 17-38% of BWTs in Caucasians, whereas no such studies have been conducted in East-Asians. Carriers with WT1 mutations are increasing because of improved survival.
  
  
  METHODS
  Statuses of WT1 and IGF2 were examined in 45 BWTs from 31 patients with WT1 sequencing and SNP array-based genomic analyses. The penetrance rates were estimated in WT1-mutant familial Wilms tumours collected from the present and previous studies.
  
  
  RESULTS
  We detected WT1 abnormalities in 25 (81%) of 31 patients and two families, which were included in the penetrance rate analysis of familial Wilms tumour. Of 35 BWTs from the 25 patients, 31 had small homozygous WT1 mutations and uniparental disomy of IGF2, while 4 had large 11p13 deletions with the retention of 11p heterozygosity. The penetrance rate was 100% if children inherited small WT1 mutations from their fathers, and 67% if inherited the mutations from their mothers, or inherited or had de novo 11p13 deletions irrespective of parental origin (P=0.057).
  
  
  CONCLUSIONS
  The high incidence of WT1 abnormalities in Japanese BWTs sharply contrasts with the lower incidence in Caucasian counterparts, and the penetrance rates should be clarified for genetic counselling of survivors with WT1 mutations.
authors: 1] Department of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama 362-0806, Japan [2] Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: Y
authors: Y
authors: Kaneko
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: H
authors: H
authors: Okita
authors: 1] Department of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama 362-0806, Japan [2] Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: M
authors: M
authors: Haruta
authors: Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-Ku, Tokyo 104-0045, Japan.
authors: Y
authors: Y
authors: Arai
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: T
authors: T
authors: Oue
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: Y
authors: Y
authors: Tanaka
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: H
authors: H
authors: Horie
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: S
authors: S
authors: Hinotsu
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: T
authors: T
authors: Koshinaga
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: A
authors: A
authors: Yoneda
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: Y
authors: Y
authors: Ohtsuka
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: T
authors: T
authors: Taguchi
authors: Japan Wilms Tumor Study Group (JWiTS), Itabashi-Ku, Tokyo 173-8610, Japan.
authors: M
authors: M
authors: Fukuzawa
mesh_terms: D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: C035170:IGF2 protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human; D007335:Insulin-Like Growth Factor II