CYTOGENETIC ASPECTS OF PEDIATRIC GERM-CEL L TUMORS

We have performed in situ hybridization (ISH) studies predominantly on paraffin sections and on isolated nuclei of 22 pediatric germ cell tu mors (GCTs) from 18 patients including 4 recurrences from three patien ts. In addition, we performed conventional cytogenetic analyses in thr ee tumor samples. Because reports on cytogenetic studies in pediatric GCTs are scarce we focused our studies on those chromosome abnormaliti es frequently observed in adult GCTs. These included numeric and struc tural abnormalities of chromosomes 1 and 12 (e.g. isochromosome 12p) a nd numeric deviations of chromosomes 8, 10, X and Y. The histological subsets of the tumors investigated included two dysgerminomas (DGE), o ne seminoma (SE), one combined seminoma, two embryonal carcinomas (EC) , two recurrent ECs, six pure yolk sac tumors (YST), five combined ter atomas, one immature teratoma (IT) and two recurrences of IT, and thre e differentiated teratomas (TD). Similar to the GCTs in adults, additi onal copies of chromosome 12 were the most frequently observed numeric abnormalities. The analysis of two paraffin-embedded tumors suggested that changes in the size of the pericentromeric hybridization signals of chromosome 12 may be attributed to the presence of i(12)(p10). Thi s was confirmed following the karyotype analysis of one EC which unequ ivocally revealed the presence of two i(12)(p10). Interestingly, using these probes, no chromosomal abnormalities were found in the pure TD or in the TD cells of mixed tumors containing a YST component. In the YST portion, however, the 1p deletions and/or numeric chromosome chang es were present. Surprisingly, deletions at the short arm of chromosom e 1, del(1)(p36.3), were frequently observed in malignant pediatric GC Ts and were the sole abnormality detected in one case. The 1p36 deleti ons were present not only in all stage IV ECs and YSTs investigated, b ut occurred also in some stage I YSTs and were always absent in the re latively benign TDs. Our results indicate that deletions at 1p36 play a role in the differentiation capacity and may serve as a prognostic m arker in pediatric GCTs.