Maintenance of normal imprinting of H19 and IGF2 genes in neuroblastoma.
H19 and insulin-like growth factor II (IGF2) are among a few genes which have been confirmed to be imprinted in normal human embryonal tissues. This results in monoallelic expression of maternal H19 and paternal IGF2. Loss of imprinting of these genes producing biallelic expression has been observed in Wilm's tumor and embryonal rhabdomyosarcoma, suggesting that an epigenetic change of DNA, in addition to a genetic change in oncogene(s) and/or tumor suppressor gene(s), may be involved in the development of these childhood cancers. Neuroblastoma, which is an embryonal tumor originating from neural crest-derived cells, occasionally occurs in individuals with the Beckwith-Wiedemann syndrome; Wilm's tumor and embryonal rhabdomyosarcoma occur even more frequently in the Beckwith-Wiedemann syndrome; and paternal uniparental disomy of H19 and IGF2 loci (chromosome 11p15) is present in the Beckwith-Wiedemann syndrome. Furthermore, neuroblastoma cell lines express IGF2, and autocrine/paracrine effects of IGF2 have been demonstrated in these cells. Thus, we examined for imprinting of both H19 and IGF2 in primary untreated neuroblastomas using the RsaI and ApaI polymorphisms within these genes, respectively. Seven of 15 tumors were informative for H19 and for IGF2, and all of these cases showed monoallelic expression of both of these genes. These results indicate that loss of imprinting of H19 and IGF2 does not occur in neuroblastomas.
Wada
M
M
Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine 90048, USA.
Seeger
R C
RC
Mizoguchi
H
H
Koeffler
H P
HP
D001483:Base Sequence; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II