Expression of insulin-like growth factor-II transcripts in Wilms' tumour

Abstract

Wilms' tumour probably arises from embryonal kidney cells and occurs in both hereditary and sporadic forms. Knudson and Strong have suggested that both forms of the disease are initiated by two mutational events. In the case of the inherited form, cytogenetic evidence indicates that a germline deletion of chromosome band 11p13 may correspond to one of the two mutations. DNA mapping evidence is consistent with the notion that the tumour susceptibility gene (Wg) on chromosome 11 is actually recessive. Comings has proposed that the dominantly inherited tumours may arise by the inactivation or loss of a diploid pair of regulatory genes which normally suppress the expression of a structural transforming gene (Tg). It has recently been suggested that the N-myc oncogene may serve as a transforming gene in retinoblastoma, although no such gene has yet been identified in Wilms' tumour. We now report that in four cases of Wilms' tumour, insulin-like growth factor-II (IGF-II) transcripts are highly elevated compared with the adjacent normal kidney. In addition, we have mapped the gene for IGF-II to chromosome band 11p14.1, which is in the immediate vicinity of Wg. These findings suggest that IGF-II may be involved in the aetiology of Wilms' tumour.

Aberrant imprinting of the insulin-like growth factor II receptor gene in Wilms' tumor

“…It is usually diagnosed in the ®rst 5 years of life. At the time of resection, these tumors express IGF2 at levels characteristic of fetal tissues, which are much higher than those found in the surrounding normal kidney (Reeve et al, 1985;Scott et al, 1985). This overexpression may, at least in part, be related to disruption of the parental genomic imprinting of the IGF2 gene.…”

Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation

“…Wilms tumours provided an ideal tumour to investigate this question because they demonstrate relaxed IGF2 imprinting (Ogawa et al, 1993;Rainier et al, 1993) at a high frequency and express IGF2 at high levels (Reeve et al, 1985). Furthermore, because approximately one third of Wilms tumours lose maternal alleles from the chromosome 11p15.5 region, methylation patterns may be readily assigned to the remaining paternally derived IGF2 gene.…”

Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers

“…Overproduction of these potent growth factors has been reported in established tumours of the breast, kidney and liver (Reeve et al, 1985;Haselbacher et al, 1987;Foekens et al, 1989;Singh et al, 1990) and IGFs are implicated in tumour development (Cullen et al, 1991). Thus, in Beckwith Weidemann syndrome, in which the IGF-II gene is effectively overexpressed, there is an excess of tumours in childhood (Weidemann, 1983;Truleau et al, 1984).…”