Evidence for divergence of DNA copy number changes in serous, mucinous and endometrioid ovarian carcinomas

Abstract

Summary Comparative genomic hybridization was applied to detect and map changes in DNA copy number in 24 well or moderately differentiated epithelial ovarian carcinomas (eight serous, eight mucinous and eight endometrioid carcinomas). Twenty-three of the 24 tumours showed changes in DNA copy number in one or several regions (median 4, range 1-17). Gains were more frequent than losses (ratio 1.6:1.0). The most frequent gains occurred in chromosomes 1 q (38%), 2p (29%), 7q (25%), 8q(38%) and 1 7q (38%), and the most common losses were located in chromosomes 8p (21%), 9p (25%) and 13q (21%). High-level amplifications were detected in seven tumours at 1q22-32, 2p15-22, 3qcen-23, 6p21-22 and 8q. In the three histological subtypes the copy number karyotypes showed substantial differences. Gains at 1 q were observed in endometrioid (five cases) and serous tumours (four cases). Increased copy number at 1 Oq was seen in endometrioid tumours only (four cases), whereas gains at 11q occurred mostly in serous tumours (four cases). In mucinous tumours, the most common copy number change was a gain at 1 7q (six cases). The results show that, in epithelial ovarian carcinoma, changes in DNA copy number are a rule rather than an exception, chromosomes 1, 2, 7, 8, 9, 13 and 17 being the most frequently affected. The diverging pattern of genetic changes seen in epithelial ovarian carcinomas with different histological phenotypes suggests that various pathways may lead to tumorigenesis and/or progression in these subgroups.

Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation

“…The cytogenetic abnormalities detected by the present study reflect many of those previously identified in other histological subtypes of ovarian cancer (Sonoda et al, 1997;Tapper et al, 1997). No genetic change unique to the clear cell histology was identified.…”

“…Comparative genomic hybridisation performed on 18 cases identified frequent deletions of chromosome 9p, 1p, 11q and 16p/q and amplifications of 3 and13q. Analysis of the three main histological ovarian subtypes (serous, mucinous and endometrioid) has demonstrated distinct karyotypes with gains at 17q more frequent in mucinous tumours with gains at 1q, 10q and 11q seen more commonly in serous and endometrioid tumours (Tapper et al, 1997). However, CGH analysis of fallopian tube carcinoma has demonstrated similarities with serous carcinoma of both uterus and ovary (Pere et al, 1998).…”

“…It is not clear whether this reflects differences in the diagnostic criteria used to define the clear cell phenotype in Japan, or differences in the molecular genetics of ovarian cancer in Japanese women. Other CGH studies of ovarian cancer of all histological subtypes have identified deletions of chromosome 9p; a study of 24 cases of grade 1 or 2 ovarian cancers reported 9p loss in six cases (25%; (Tapper et al, 1997)). A larger study of 106 cases of all histological grades identified 9p loss in 41% of patients (Kiechle et al, 2001).…”

“…Comparative genomic hybridisation has detected aberrations that correlate with ovarian tumour grade including deletions at chromosome 11p and 13q, and amplifications at 8q and 7p in poorly differentiated tumours as compared with 12p deletions and 18p amplifications in well-and moderately differentiated tumours (Kiechle et al, 2001). Some evidence suggests that the main different histological subtypes (serous, mucinous and endometrioid) have different copy number karyotypes, with gains more frequently noted at 10q and 11q in endometrioid and serous tumours respectively and at 17q in mucinous tumours (Tapper et al, 1997).…”

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

“…A variety of solid tumours show ampli®cation of 1q21-q22, e.g. 70 ± 80% of hepatocellular carcinomas and 25 ± 30% of ovarian cancers (Tapper et al, 1998;Wong et al, 1999;Zimonjic et al, 1999). Although gain of the whole long arm (1q) is most frequent in breast cancers, local ampli®cation a ecting 1q21-q22 has been observed (Tirkkonen et al, 1998).…”