Comparative genomic hybridization of microdissected familial ovarian carcinoma: two deleted regions on chromosome 15q not previously identified in sporadic ovarian carcinoma.
The vast majority of familial ovarian cancers harbor a germline mutation in either the breast cancer gene BRCA1 or BRCA2 tumor suppressor genes. However, mutations of these genes in sporadic ovarian cancer are rare. This suggests that in contrast to hereditary disease, BRCA1 and BRCA2 are not commonly involved in sporadic ovarian cancer and may indicate that there are two distinct pathways for the development of ovarian cancer. To characterize further differences between hereditary and sporadic cancers, the comparative genomic hybridization technique was employed to analyze changes in copy number of genetic material in a panel of 36 microdissected hereditary ovarian cancers. Gains at 8q23-qter (18 of 36, 5 cases with high-level amplifications), 3q26.3-qter (18 of 36, 2 cases with high-level amplifications), 11q22 (11 of 36) and 2q31-32 (8 of 36) were most frequent. Losses most frequently occurred (in decreasing order of frequency) on 8p21-pter (23 of 36), 16q22-pter (19 of 36), 22q13 (19 of 36), 9q31-33 (16 of 36), 12q24 (16 of 36), 15q11-15 (16 of 36), 17p12-13 (14 of 36), Xp21-22 (14 of 36), 20q13 (13 of 36), 15q24-25 (12 of 36), and 18q21 (12 of 36). Comparison with the literature revealed that the majority of these genetic alterations are also common in sporadic ovarian cancer. Deletions of 15q11-15, 15q24-25, 8p21-ter, 22q13, 12q24 and gains at 11q22, 13q22, and 17q23-25, however, appear to be specific to hereditary ovarian cancer. Aberrations at 15q11-15 and 15q24-25 have not yet been described in familial ovarian cancer. In these regions, important tumor suppressor genes, including the hRAD51 gene, are located. These and other yet unknown suppressor genes may be involved in a specific carcinogenic pathway for familial ovarian cancer and may explain the distinct clinical presentation and behavior of familial ovarian cancer.
Zweemer
R P
RP
Department of Obstetrics and Gynaecology, VU Medical Center, Amsterdam, The Netherlands. rp.zweemer.humgen@med.vu.nl
Ryan
A
A
Snijders
A M
AM
Hermsen
M A
MA
Meijer
G A
GA
Beller
U
U
Menko
F H
FH
Jacobs
I J
IJ
Baak
J P
JP
Verheijen
R H
RH
Kenemans
P
P
van Diest
P J
PJ
D024682:BRCA2 Protein / Q000235:genetics; D002884:Chromosomes, Human, Pair 15; D005260:Female; D019398:Genes, BRCA1; D005819:Genetic Markers; D006801:Humans; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000235:genetics*; D017384:Sequence Deletion
D024682:BRCA2 Protein; D005819:Genetic Markers