Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour

Abstract

Genomic imprinting has been implicated in the onset of several embryonal tumours but the mechanism is not well understood. Maternal chromosome 11p15 loss of heterozygosity and paternal chromosome 11 isodisomy suggest that imprinted genes are involved in the onset of Wilms' tumour and the Beckwith-Wiedemann syndrome. The insulin-like growth factor II (IGF2) gene located at 11p15.5 has been put forward as a candidate gene as it is maternally imprinted (paternally expressed) in the mouse, and is expressed at high levels in Wilms' tumours. We report here that the IGF2 gene is expressed from the paternal allele in human fetal tissue, but that in Wilms' tumour expression can occur biallelically. These results provide, to our knowledge, the first evidence that relaxation of imprinting may play a role in the onset of disease and suggest a new genetic mechanism involved in the development of cancer.

Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin

“…The common expression patterns in TGCTs were biallelic expression of H19 and null expression of IGF2 in the present study (Table 1). The patterns of H19/IGF2 expression were in contrast to those in Wilms' tumors (Ogawa et al, 1993;Rainier et al, 1993;Moulton et al, 1994;Steenman et al, 1994;Taniguchi et al, 1995;Feinberg and Tycko, 2004).…”

“…Epigenetic alterations in the 11p15.5 imprinted gene cluster are frequent in human cancers and are associated with disordered imprinting of IGF2 and H19 (Ogawa et al, 1993;Rainier et al, 1993;Moulton et al, 1994;Steenman et al, 1994;Taniguchi et al, 1995;Feinberg and Tycko, 2004). Loss of imprinting leads to pathological biallelic expression of IGF2 in Wilms' tumors (Ogawa et al, 1993;Rainier et al, 1993).…”

“…Loss of imprinting leads to pathological biallelic expression of IGF2 in Wilms' tumors (Ogawa et al, 1993;Rainier et al, 1993). This abnormality in Wilms' tumors is inevitably linked to a gain in methylation, localized to the 5 0 sequences and transcribed region of the closely linked and reciprocally imprinted H19 gene (Moulton et al, 1994;Steenman et al, 1994;Taniguchi et al, 1995).…”

“…The results of IGF2 genotyping are shown in Table 1. Sequences of the primer pair were (Ogawa et al, 1993): IGF2P2, 5 0 -CTTGGACTTTGAGTCAAATTGG (8703-8724, X03562); IGF2P3, 5 0 -GGTCGTGCCAATTACATTTCA (940 646-940 666, NT009237). Accession number and corresponding nucleotide number of each primer are shown within parenthesis.…”

Loss of imprinting and allele switching of p73 in renal cell carcinoma

“…Since then it has been described in several imprinted genes, including IGF2, HI9, IPW, and p57KIP2 (Ogawa et al, 1993;Hibi et al, 1996;Rachmilewitz et al, 1996;Thompson et al, 1996). LOI involving IGF2 or/and H19 has been reported in about 14 di erent types of tumors (reviewed by McBride 1997; Oda et al, 1998).…”