Plasmacytomas can be induced in BALB/c mice by three different agents: (1) Mineral oil, (2) Solid plastics such as diffusion chambers, and (3) Abelson murine leukemia virus plus pristane. We examined chromosome aberrations in mouse plasmacytomas induced by each of the three agents. Most of plasmacytomas showed the specific translocations of chromosomes between either No. 12 and No. 15 or No. 6 and No. 15. These chromosome translocations were common to all plasmacytomas induced by different agents. The specific breakpoints were at 12F2 where IgH genes appear to locate, and 6C2 where kappa light chain genes might be located, and 15D2/3 where c-myc oncogene appears to locate. However, we have found very recently a few plasmacytomas which have no translocations of chromosomes. The subregion (s) of one copy of chromosome 15 which is called D1:D2 appears to be deleted in these plasmacytomas. In the next study, we examined the relationship of chromosomal aberrations to the activation of c-myc oncogene. Not only the plasmacytomas with chromosome translocations, but also the translocation-negative plasmacytomas showed the either rearrangement or germline type of c-myc DNA. Rearranged c-myc transcript was found only in plasmacytomas with the 12;15 translocation. However, not all plasmacytomas belonging to this group expressed the altered c-myc RNA transcript. Our experiments indicated that the germline type c-myc RNA was 2.4 kb and the rearranged c-myc RNA was mostly 1.8 kb in length. Concerning the c-myc DNA, the germline type was 21 kb and the rearranged type of c-myc DNA was estimated, mostly, to be 14 kb by EcoRI digestion.

Complete mole is an abnormal human pregnancy which is characterized by grossly swollen villi in the absence of a fetus. It has been widely accepted that of all forms of pregnancy that leads to choriocarcinoma, the risk associated with moles is by far the highest, being 2000 to 4000 times greater than that of normal pregnancy or abortion (1). However there has been no direct proof that choriocarcinoma indeed derives from complete mole. In the present study, to shed some light on the genesis of trophoblastic tumor, chromosome, HLA and PGM1 polymorphisms were examined for complete moles and choriocarcinomas. As a result, it has been ascertained that complete mole was androgenetic in origin; the entire genome of the molar conceptus was paternally derived. More than ninety percent of cases were resulted from fertilization of an empty egg (i.e. the nucleus was either eliminated or inactivated) by a haploid sperm. The paternally derived haploid set then duplicated without cytokinesis and restored diploidy. This class of moles had invariably a 46, XX karyotype and was completely homozygous for any genetic markers. Fertilization of an empty egg by two spermatozoa could elucidate remaining cases. The androgenetic origin of complete mole has provided us with a means to directly evaluate the relationship between choriocarcinomas and their putative forerunners; complete homozygosity and exclusive inheritance of a paternal genome would be expected if the tumor arose from complete mole derived from the former mechanism. However, the heterozygosity observed in choriocarcinoma cells suggested that the tumor did not arise from moles which originated from the fertilization of an empty egg by a haploid sperm.(ABSTRACT TRUNCATED AT 250 WORDS)