Ryuji Fukuzawa، نويسنده , , Norman E Breslow، نويسنده , , Ian M. Morison MB ChB، نويسنده , , Patrick Dwyer، نويسنده , , Takeshi Kusafuka، نويسنده , , Yasutsugu Kobayashi، نويسنده , , David MO Becroft، نويسنده , , J Bruce Beckwith، نويسنده , , Elizabeth J Perlman، نويسنده , , Anthony E Reeve، نويسنده ,
Variations in the international incidence of Wilmsʹ tumour might be due to genetic factors. The maternal insulin-like growth factor 2 gene (IGF2) is imprinted in normal tissues, whereas in some Wilmsʹ tumours and other tumour types the imprint is lost, leading to biallelic transcription of IGF2. We investigated whether the difference in incidence of Wilmsʹ tumour between children of east-Asian descent and white children is due to variations in proportion of tumours with loss of IGF2 imprinting (IGF2 LOI).
We assessed IGF2 LOI by use of an ApaI polymorphism in IGF2 exon 9 or quantitative PCR measuring DNA methylation of the H19 and KvDMR1 alleles. The frequencies of perilobar nephrogenic rests associated with Wilmsʹ tumour were assessed histologically in Japanese children and children of white and east-Asian descent.
IGF2 LOI was present in Wilmsʹ tumours from predominantly white children from New Zealand (13 of 41tumours) but absent in tumours from Japanese children (0 of 21 tumours; difference in proportions 0•32, 95% CI 0•07–0•52). Frequency of perilobar nephrogenic rests accompanying tumours from white American children (1192 of 5002, 24%) was significantly higher than in Japanese (one of 56, 1%, difference in proportions 0•22, 95% CI 0•14–0•25) and east-Asian American children (seven of 92, 8%, 0•16, 0•09–0•21).
Wilmsʹ tumours in the east-Asian population rarely arise from the IGF2 LOI mechanism frequently noted in white patients. Our findings that IGF2 LOI and perilobar nephrogenic rests associated with this mechanism arise at low frequency in Japanese and east-Asian American children lend support to this conclusion. Variation in frequency of this epigenetic mechanism provides one explanation for the difference in incidence of Wilmsʹ tumour between populations.