Involvement of IGF(2) and H(19) imprinting in choriocarcinoma development.

Complete hydatidiform mole is an abnormal pregnancy characterized by grossly swollen villi in the absence of a fetus (Kajii and Ohama 1997, Wake et al., 1978, Jacobs et al., 1980). It is well known that this abnormal pregnancy product is androgenetic in origin. The entire genome of the molar conceptus is paternally derived. The majority of moles result from fertilization of an empty egg by haploid sperm. The paternally derived haploid set then duplicated without cytokinesis and restores diploidy. Invariably, this class of moles has a 46, XX karyotype and is completely homozygous for genetic markers. Fertilization of an empty egg by two sperms is responsible for the remaining case. These moles show a mixture of homozygous and heterozygous patterns of paternally derived genetic markers. Although complete mole is usually a benign process, 10 to 20 percent of cases leads to either invasive mole or choriocarcinoma. This propensity to malignancy has to associate with the genetic features shown in the mole, that imply the formation of homozygosity and the selective inheritance of paternal genome. It has been described in various human malignancies that both genetic features associate with the inactivation of tumor suppressor genes. Homozygosity would lead to the inactivation of tumor suppressor gene in the mole by a signal event occurred on sperm DNAs. In turn, paternal transmission would result in the silencing of particular tumor suppressor genes. Thus, tumor suppressor genes inactivated either by homozygosity formation or by paternal transmission would be involved in the pathogenesis of choriocarcinoma. Both the maternal and paternal genomes are necessary for normal embryonic development in mammals. Parental-origin-specific functional differences between two alleles, known as genomic imprinting, seem to be exploited for a regulatory mechanism crucial for the proper development of both embryonic and extraembryonic tissues. The list of imprinted genes identified is growing rapidly lately in mouse and man (DeChiara TM et al., 1991, Barlow et al., 1991, Bartolomei MS et al., 1991, Leff SE et al., 1992, Hatada I et al., 1993, Giddings SJ et al., 1994, Hayashizaki Y et al., 1994, Villar AJ et al., 1994, Guillemot F et al., 1995). Among these, IGF2 and H19 tightly linked on human chromosome 11 are of special interest because of their reciprocal imprinting and possible association with certain malignancy and congenital abnormalies. The IGF2 gene expressed from the paternally derived allele (Ohlsson et al., 1993, Giannoukalis et al., 1993), whereas the H19 gene is expressed from the maternally derived allele (Rachmilewitz et al., 1992, Zhang et al 1993, Ferguson-Smith et al., 1993).

Wake N ，Arima T ，Matsuda T 《-》

Involvement of IGF2 and H19 imprinting in choriocarcinoma development.

Wake N ，Arima T ，Matsuda T 《INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS》

[A study for the genesis of trophoblastic tumor, with reference to its androgenetic origin].

Wake N 《-》

Association of IGF2 and H19 imprinting with choriocarcinoma development.

Arima T ，Matsuda T ，Takagi N ，Wake N ... -  《cancer genetics and cytogenetics》

Paternally derived H19 is differentially expressed in malignant and nonmalignant trophoblast.

Walsh C ，Miller SJ ，Flam F ，Fisher RA ，Ohlsson R ... -  《CANCER RESEARCH》