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 and molecular genetic techniques is limited. However, the data available to date reveal a pattern of cytogenetic aberrations different from that in adults. Comparative genomic hybridization (CGH) is a valuable technique for the genetic profiling of tumors that allows screening for chromosomal imbalances consistent with amplification of oncogenes and loss of putative tumor suppressor genes. As CGH does not require tissue culture, it also allows analysing archival tissue samples.


METHODS
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=20), ovary (n=5), CNS (n=2), and the face (n=1).


METHODS
The experimental procedure includes differential enzymatic fluorescence labeling of tumor and control DNA followed by comparative hybridization to normal male chromosomes, karyotyping and computerized analysis of the fluorescence profiles.


RESULTS
With the exception of one testicular and two ovarian tumors, malignant GCTs in children do not show chromosomal gain of 12p, which is characteristic of GCTs in adult patients. Irrespective of the primary site, childhood 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 frequency.


CONCLUSIONS
These studies will help guiding further investigations elucidating the role of putative tumor suppressor genes at e.g. 1p36 and 6q. In addition, further studies incorporated in prospective therapeutic protocols are necessary to evaluate the prognostic relevance of specific genetic aberrations.
Schneider
D T
DT
Clinic of Pediatric Hematology and Oncology, Heinrich-Heine-University, Medical Center, Düsseldorf, Germany. dominik.schneider@uni-duesseldorf.de
Schuster
A E
AE
Fritsch
M K
MK
Calaminus
G
G
Harms
D
D
Göbel
U
U
Perlman
E J
EJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016543:Central Nervous System Neoplasms / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D020732:Cytogenetic Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D018240:Endodermal Sinus Tumor / Q000235:genetics; D005153:Facial Neoplasms / Q000235:genetics; D005260:Female; D018237:Germinoma / Q000145:classification / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods; D010051:Ovarian Neoplasms / Q000235:genetics; D012189:Retrospective Studies; D012445:Sacrococcygeal Region; D013724:Teratoma / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm