Comparative genomic hybridization of microdissected familial ovarian carcinoma: Two deleted regions on chromosome 15q not previously identified in sporadic ovarian carcinoma
Rp. Zweemer et al., Comparative genomic hybridization of microdissected familial ovarian carcinoma: Two deleted regions on chromosome 15q not previously identified in sporadic ovarian carcinoma, LAB INV, 81(10), 2001, pp. 1363-1370
The vast majority of familial ovarian cancers harbor a germline mutation in
either the breast cancer gene BRCA1 or BRCA2 tumor suppressor genes. Howev
er, mutations of these genes in sporadic ovarian cancer are rare. This sugg
ests that in contrast to hereditary disease, BRCA1 and BRCA2 are not common
ly involved in sporadic ovarian cancer and may indicate that there are two
distinct pathways for the development of ovarian cancer. To characterize fu
rther differences between hereditary and sporadic cancers, the comparative
genomic hybridization technique was employed to analyze changes in copy num
ber of genetic material in a panel of 36 microdissected hereditary ovarian
cancers. Gains at 8q23-qter (18 of 36, 5 cases with high-level amplificatio
ns), 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), 1
5q11-15 (16 of 36), 17p12-13 (14 of 36), Xp21-22 (14 of 36), 20q13 (13 of 3
6), 15q24-25 (12 of 36), and 18q21 (12 of 36). Comparison with the literatu
re 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 spec
ific to hereditary ovarian cancer. Aberrations at 15q11-15 and 15q24-25 hav
e not yet been described in familial ovarian cancer. In these regions, impo
rtant tumor suppressor genes, including the hRAD51 gene, are located. These
and other yet unknown suppressor genes may be involved in a specific carci
nogenic pathway for familial ovarian cancer and may explain the distinct cl
inical presentation and behavior of familial ovarian cancer.