Insulin-like growth factor-II imprinting in cancer

To help explain these disparate findings, Little and colleaguess proposed that [Wilms]' tumours have duplicate, active paternal IGF2 genes. This double-dose model is attractive since it fits with observations that two copies of paternal 11p15 are present constitutionally in some cases of Beckwith-Wiedemann syndrome. This syndrome predisposes to Wilms' and other embryonal tumours.6 However, not all Wilms' tumours have loss of heterozygosity at 11p15; in about 50% of turnouts the normally silent maternal IGF2 allele is activated.7,8 Theoretically, tumours with loss of IGF2 imprinting and 11p15 loss of heterozygosity or reduplication may be regarded as biologically equivalent since they have the potential to give rise to a two-fold increase in IGF2 transcription (panel). In reality, confirmation of this two-fold difference is technically difficult and conflicting results have been reported; a definitive result will require analysis of many tumours to take into account the variation in tumour histology and cellular distribution of IGF2. This aspect was highlighted in the recent study by J D Ravenel and colleagues9 in which tumours with loss of IGF2 imprinting had 2.2-fold increased expression of IGF2 compared with tumours with normal imprinting.