ELSEVIER Chromosomal Abnormalities in Choriocarcinomas of the Female Eduardo Rodriguez, Jonathan Melamed, Victor Reuter, and R. S. K. Chaganti ABSTRACT: We have studied six cases of choriocarcinomas in the female by conventional cytogenetic analysis and by in situ hybridization using a 12p painting probe, and found evidence for chromosome 12 abnormalities in two of them. Abnormalities of chromosome 12 are a common occurrence in genitouri- nary tumors of the female, but their significance is not known. We discuss the present findings in relation to those in malignant ovarian germ cell tumors (MOGCTs). INTRODUCTION Choriocarcinomas in the female may result from malignant transformation of ovarian germ cells or from gestational trophoblastic disease, the latter either from trophoblasts of pregnant concepti [1] or complete hydatidiform moles [2]. Heterozygous (XY) moles derived from dispermic fertiliza- tion of empty eggs have been suggested to carry a higher potential for malignant transformation than homozygous (XX) moles derived from parthenogenetic reduplication of empty eggs fertilized by one sperm [2]. Previously, only four primary choriocarcinomas have been analyzed by cytogenetics and all showed abnormalities of chromosome 12 in the form of polysomy. In addition, one case had a del(12q) and another had an i(12)(q10) [3, 4]. In this study, we have analyzed the karyotypes of six cases of choriocarcinomas in the female by conventional banding and by in situ hybridization (ISH), using a 12p painting probe, and found chromosome 12 to be abnormal in two. MATERIALS AND METHODS Tumor Ascertainment, Cell Culture, and Cytogenetic Analysis The six tumors studied represent part of a consecutive ascer- tainment of female choriocarcinomas submitted for cyto- genetic analysis at the Memorial Sloan-Kettering Cancer Center between June 1988 and June 1993. Tumors were pro- From the Cell Biology and Genetics Program and the Cytogenetics Service, Department of Pathology, Memorial Sloan-Kettering Can- cer Center, New York, New York. This work was supported in part by NIH grants CA-05826 and CA-08748, and by The Byrne Fund. Address reprint requests to: Dr. R. S. K. Chaganti, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Received May 2Z 1994; accepted July 8, 1994. Cancer Genet Cytogenet 80:9-12 (1995) © Elsevier Science Inc., 1995 655 Avenue of the Americas, New York, NY 10010 cessed and cultured for cytogenetic analysis as previously described [5]. In Situ Hybridization A 12p painting probe generated by microdissection from metaphase spreads obtained from phytohemagglutinin- stimulated peripheral blood lymphocytes [6] was used to hy- bridize to interphase nuclei of cultured cells. As control, a chromosome I centromeric satellite probe was hybridized to separate slides of each of the cases. Hybridization and sig- nal detection of the 12p painting probe and the chromosome I centromeric probe were performed using ONCOR (Gaithers- burg, MD) reagents and protocols as described [7]. The propidium iodide-stained slides were visualized using a Nikon fluorescence microscope equipped with a B filter. To determine the sex chromosome composition of the choriocarcinomas, interphase spreads were hybridized with biotin-labeled Y chromosome centromeric satellite probe and to digoxigenin-labeled X chromosome centromeric satellite probe. Detection was performed using ONCOR (Gaithersburg, MD) reagents and protocols. RESULTS Table 1 presents the histologic, karyotypic, and in situ hy- bridization results of the six tumors studied. The choriocar- cinomas were all derived from gestational trophoblastic dis- ease. Figure I illustrates the histologic characteristics of the tumors. By cytogenetic analysis, three presented abnormal karyotypes, one was a cytogenetic failure due to the lack of tumor cell growth in culture, and in the remaining two only normal cells were found. Two of the tumors with abnormal karyotype had chromosome 12 abnormalities (Fig. 2); one had trisomy 12 (163A), and the other had a rearrangement at band 12p13 (317A). Hybridization of the 12p painting probe did not reveal extra copies of 12p in any of the cases apart from 163A which was trisomic. Specimen 317A did not re- veal extra copies of 12p. 0165-4608/95/$9.50 SSDI 0165-4608(94)00145-2