Genetic analysis of childhood germ cell tumors with comparative genomic hybridization

Background: Germ Cell Tumors (GCTs) in children and adolescents constitute a clinically and histologically heterogeneous group of tumors. Compared to GCTs in adults, the numbers of GCTs in children analyzed with cytogenetic a nd molecular genetic techniques is limited. However, the data available to date reveal a pattern of cytogenetic aberrations different from that in adu lts. Comparative genomic hybridization (CGH) is a valuable technique for th e genetic profiling of tumors that allows screening for chromosomal imbalan ces consistent with amplification of oncogenes and loss of putative tumor s uppressor genes. As CGH does not require tissue culture, it also allows ana lysing archival tissue samples. Patients: This study focuses exclusively on GCTs in children younger than ten years of age and summarizes the genetic data of 51 tumors. Eighteen teratomas and 33 malignant GCTs were included. Primary sites were the testis (n = 10), coccyx (n = 13), mediastinum (n = 2 0), ovary (n = 5), CNS (n = 2), and the face (n = 1). Methods: The experime ntal procedure includes differential enzymatic fluorescence labeling of tum or and control DNA followed by comparative hybridization to normal male chr omosomes, karyotyping and computerized analysis of the fluorescence profile s. Results: With the exception of one testicular and two ovarian tumors, ma lignant GCTs in children do not show chromosomal gain of 12p, which is char acteristic of GCTs in adult patients. Irrespective of the primary site, chi ldhood GCTs show chromosomal imbalances of chromosome 1 (loss of distal 1p, gain of 1q), deletion of 4q and 6q as well as gain of 20q at a high freque ncy. Conclusions: These studies will help guiding further investigations el ucidating the role of putative tumor suppressor genes at e.g. 1p36 and 6q. In addition, further studies incorporated in prospective therapeutic protoc ols are necessary to evaluate the prognostic relevance of specific genetic aberrations.