Equivalent expression of paternally and maternally inherited WT1 alleles in normal fetal tissue and Wilms' tumours.
Observations of non-random maternal 11p allele loss in Wilms' tumour (WT) have implied the possible involvement of an imprinted 11p locus in WT aetiology. A proposed 11p13 Wilms' tumour gene, WT1, has recently been isolated and encodes a zinc finger DNA-binding protein, the 3' untranslated region of which contains a polymorphic dinucleotide repeat (CA repeat) motif. We have exploited this transcribed CA repeat to examine the allelic expression pattern of WT1 and thereby determine whether transcriptional imprinting of this gene occurs. DNA and reverse-transcribed RNA from tumours and normal tissue were subjected to the polymerase chain reaction (PCR) using radiolabelled primers flanking the CA repeat. The gene was seen to be expressed from both of the constitutive alleles in 9-week human fetal kidney, all informative Wilm's tumours and neonatal kidney tissue adjacent to the tumours. In one tumour, known to be heterozygous for a point mutation in zinc finger 2, direct sequencing confirmed that both mutant and wild-type transcripts were being expressed. These results demonstrate that this gene is not subject to transcriptional imprinting in tumours or normal fetal kidney.
Little
M H
MH
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Dunn
R
R
Byrne
J A
JA
Seawright
A
A
Smith
P J
PJ
Pritchard-Jones
K
K
van Heyningen
V
V
Hastie
N D
ND
D000483:Alleles; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D007173:Imprinting, Psychological; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025721:WT1 Proteins