Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization.
The limited information available to date regarding the genetic alterations in germ cell tumors of the central nervous system has raised concerns about their biologic relationship to other germ cell tumor entities. We investigated fresh-frozen or archival tumor samples from 19 patients with central nervous system germ cell tumors (CNS-GCTs), including seven germinomas, eight malignant nongerminomatous germ cell tumors and four teratomas, using chromosomal comparative genomic hybridization to determine recurrent chromosomal imbalances. All 15 malignant CNS-GCTs and two of four teratomas showed multiple chromosomal imbalances. Chromosomal gains (median: 4 gains/tumor, range: 0-9 gains/tumor) were observed more frequently than losses (median: 1.6 losses/tumor, range: 0-6 losses/tumor). Gain of 12p, which is considered characteristic for germ cell tumors of the adult testis, was detected in 11 of 19 tumors and 10 of 15 malignant CNS-GCTs. In one tumor, gain of 12p was confined to an amplicon at 12p12, corresponding to the commonly amplified region on 12p. Other common gains were found on chromosome arms 1q and 8q (n = 9, each). Among the chromosomal losses, parts of chromosome 11 (n = 5), 18 (n = 4), and 13 (n = 3) were deleted most frequently. Notably, we observed no difference in the genetic profiles of germinomatous and nongerminomatous CNS-GCTs; however, the average number of imbalances was higher in the latter group. A meta-analysis comparing 116 malignant gonadal and extragonadal germ cell tumors revealed that the genomic alterations in CNS-GCTs are virtually indistinguishable from those found in their gonadal or other extragonadal counterparts of the corresponding age group. These data strongly argue in favor of common pathogenetic mechanisms in gonadal and extragonadal germ cell tumors.
Schneider
Dominik T
DT
Clinic of Paediatric Oncology, Haematology and Immunology, Heinrich-Heine-University, Düsseldorf, Germany. dominik.schneider@uni-dusseldorf.de
Zahn
Susanne
S
Sievers
Sonja
S
Alemazkour
Katayoun
K
Reifenberger
Guido
G
Wiestler
Otmar D
OD
Calaminus
Gabriele
G
Göbel
Ulrich
U
Perlman
Elizabeth J
EJ
D000293:Adolescent; D000328:Adult; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015201:Meta-Analysis as Topic; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*
D004273:DNA, Neoplasm