Epigenetic lesions at the H19 locus in Wilms' tumour patients.
To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal kidney levels. Of the expression-negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non-neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.
Moulton
T
T
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Crenshaw
T
T
Hao
Y
Y
Moosikasuwan
J
J
Lin
N
N
Dembitzer
F
F
Hensle
T
T
Weiss
L
L
McMorrow
L
L
Loew
T
T
Kraus
W
W
Gerald
W
W
Tycko
B
B
D000483:Alleles; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008745:Methylation; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D009396:Wilms Tumor / Q000235:genetics*
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007335:Insulin-Like Growth Factor II