Altered imprinting, promoter usage, and expression of insulin-like growth factor-II gene in gestational trophoblastic diseases.
OBJECTIVE
We aimed to understand the involvement of imprinted genes in the pathogenesis of gestational trophoblastic diseases (GTD) such as hydatidiform mole (H-mole) and gestational trophoblastic tumors (GTT).


METHODS
An allelic-typing assay was performed using a PCR-RFLP-based method for identification of heterozygous informative cases. The usage of insulin-like growth factor-II (IGF2) promoters was examined by RT-PCR using promoter-specific primers. The mRNA expression of IGF2 and H19 was quantified using a densitometer.


RESULTS
The imprinting of IGF2 and H19 was maintained in all normal placenta tissues (n = 15) but relaxed in GTD (n = 47). Loss of imprinting (LOI) of IGF2 was in the order of GTT (57%) > complete H-mole (43%) > partial H-mole (25%). Similarly, LOI of H19 was in the order of GTT (40%) > complete H-mole (18%) > partial H-mole (0%). Promoter usage pattern of IGF2 changed with gestation stage of normal placentae and GTD. In normal placentae, the usage of promoter P1 was higher than that of P4 in the first trimester but lowered in the full term. H-mole and GTT predominantly used promoter P1 with relative silencing of promoter P4. Although normal early placenta and various GTD tissues showed the similar usage of IGF2 promoter P1, GTT tissues revealed the higher expression levels of IGF2 but a down-regulation of H19 relative to the normal early placentae.


CONCLUSIONS
These results suggest that LOI, deregulation of IGF2 promoters, and the altered expression levels of IGF2 and H19 genes might be associated with the progression of GTD.
Kim
Sung Jo
SJ
Comprehensive Gynecologic Cancer Center, Pundang CHA General Hospital, Sungnam, Kyonggi-do, South Korea.
Park
Sang Eun
SE
Lee
Chan
C
Lee
Sun Young
SY
Kim
In Ho
IH
An
Hee Jung
HJ
Oh
Yu-Kyoung
YK
D000483:Alleles; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D031901:Gestational Trophoblastic Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II