Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour.
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.
Ogawa
O
O
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Eccles
M R
MR
Szeto
J
J
McNoe
L A
LA
Yun
K
K
Maw
M A
MA
Smith
P J
PJ
Reeve
A E
AE
D000483:Alleles; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D004277:DNA, Single-Stranded; D004303:Dosage Compensation, Genetic; D005220:Fathers; D005260:Female; D005333:Fetus; D006579:Heterozygote; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009035:Mothers; D012150:Polymorphism, Restriction Fragment Length; D012334:RNA, Neoplasm / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics*
D004277:DNA, Single-Stranded; D012334:RNA, Neoplasm; D007335:Insulin-Like Growth Factor II