DNA copy number changes in malignant ovarian germ cell tumors.
Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.
Kraggerud
S M
SM
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Olso.
Szymanska
J
J
Abeler
V M
VM
Kaern
J
J
Eknaes
M
M
Heim
S
S
Teixeira
M R
MR
Tropé
C G
CG
Peltomäki
P
P
Lothe
R A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004407:Dysgerminoma / Q000235:genetics*; D018240:Endodermal Sinus Tumor / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007621:Karyotyping; D008875:Middle Aged; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000235:genetics*; D013724:Teratoma / Q000235:genetics*