Loss of H19 imprinting and up-regulation of H19 and SNRPN in a case with malignant mixed Müllerian tumor of the uterus.
In several human cancers, it has been recently reported that abnormally altered status of genomic imprinting is related to oncogenesis. In this study, we investigated the expression of three imprinted genes in a case with malignant mixed Müllerian tumor of the uterus (MMMT). In the tumor, expression of H19 showed marked upregulation (6.3-fold) with biallelic expression compared with that in the corresponding normal myometrium. The 5'-promoter region of H19 was hypomethylated in the tumor, whereas it was hemimethylated in the myometrium. Expression of the small nuclear ribonucleoprotein polypeptide N gene (SNRPN) was also upregulated by 1.9-fold. However, the insulin-like growth factor II gene (IGF2) was expressed at low levels in both myometrium and MMMT. The overexpression of H19 is caused by reactivation of the repressed allele of H19 due to demethylation of CpG islands within its 5'-promoter region. Whether upregulation of SNRPN is caused by its biallelic expression remains undetermined because restriction fragment length polymorphisms (RFLP) sites were not informative in SNRPN and IGF2. In conclusion, H19 and SNRPN may play significant roles in the tumorigenesis of MMMT and H19 may have tumor-promoting activity in addition to its known tumor-suppressing activity, probably depending on the tissue and the local milieu.
Hashimoto
K
K
Department of Obstetrics and Gynecology, Osaka University Medical School, Osaka Saiseikai Nakatsu Hospital, Kita-ku, Japan.
Azuma
C
C
Tokugawa
Y
Y
Nobunaga
T
T
Aki
T A
TA
Matsui
Y
Y
Yanagida
T
T
Izumi
H
H
Saji
F
F
Murata
Y
Y
D001324:Autoantigens / Q000235:genetics*; D015152:Blotting, Northern; D019175:DNA Methylation; D004273:DNA, Neoplasm; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000235:genetics* / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology; D055517:snRNP Core Proteins
D001324:Autoantigens; D004273:DNA, Neoplasm; C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins