Karyotypic information was obtained on 86 of the original 110 samples (Additional file 1: Table S1). The 24 cultures that failed showed either no cell attachment after several days in vitro or no metaphases. A normal karyotype was found in 22 tumors. The remaining 64 tumors (Additional file 1: Table S1) mostly showed complex karyotypes with several structural and numerical aberrations. Simple karyotypes, by which we mean karyotypes showing less than four aberrations, were seen only in one high-grade serous carcinoma (case 35), two low-grade serous carcinomas (cases 77 and 78), one clear-cell carcinoma (case 102), and one mixed endometrioid and mucinous carcinoma (case 107). Case 35 (a high-grade serous tumor) showed monosomies of chromosomes X, 4, and 10. Case 77 (a low-grade serous tumor) showed two unrelated clones with monosomy 11 and monosomy of the X chromosome, respectively. Case 78 (a low-grade serous tumor) showed trisomy 7 as the sole abnormality in all cells analyzed. Case 102 (a clear-cell tumor) had two supernumerary markers of unknown origin in three metaphases of the 45 cells analyzed. Case 107 (also a mixed endometrioid and mucinous carcinoma) showed additional material of unknown origin on 8q24 as the sole chromosomal abnormality. The only tumor showing obvious clonal evolution (i.e., beyond having several aberrations) was case 38 (a high-grade serous carcinoma) which had three related clones with only numerical aberrations corresponding to the karyotype 47 ~ 49,XX,+8,+9[2]/49,idem,+5,-6,+7[4]/54,idem,+3,+5,+6,+7,+14,+17,+19[5]. Breakpoint clusters were seen at chromosome arms 11q (33 out of altogether 431 breaks, 7.65%), 19p (27 breaks; 6.26%), and 19q (22 breaks; 5.1%). The aberrations involving these chromosomes were of different types, e.g., deletions, translocations, and additions of unknown material. Although simple rearrangements between two chromosomes could be described in some tumors, in the majority of cases it was not possible to identify the partner chromosome in the rearrangement which led us to resort to descriptions such as add(11)(p/q) and/or add(19)(p/q).
The HR-CGH analysis of genomic imbalances showed gains and/or losses in 81 tumors (Additional file 1: Table S1), whereas no imbalances were scored in seven samples. No informative results were obtained in another seven tumors due to poor quality of hybridization signals. In the remaining 15 cases, no DNA was available to perform the analysis. Gains were more frequent than losses and amplifications, i.e., more than four-fold gains, were scored in 30 tumors (21 high-grade serous carcinomas, four endometrioid, two clear-cell, one low-grade serous, one mucinous, and one undifferentiated carcinoma). The high-grade serous carcinomas (n = 56 with imbalances) mostly showed gains of 3q26-27 (detected in 25% of the tumors with imbalances), followed by gains of 3q24-25 and 8q23 (in 23%), and 1q31-32, 3q23, 3q28, 7q31-32, 8q24, and 12p12 (all detected in 21% of the tumors; Figure 1). The most frequent losses were scored at 17p12 (21%), 17p11, 17p13, and 22q12-13 (20%), and 5q14, 6q24, and 16q22 (18%). The endometrioid carcinomas (n = 12 with imbalances) showed gains of 1q23 (83% of the endometrioid tumors with imbalances), followed by 1q24 and 8q22 (75%), 1q32 (67%), 1q21-22, 1q25-31, 1q41-42, 8q13-21, and 8q23q24 (58%), and 2q23-24, 3q13, 3q25-26, 6p12, 8q12, and 20p11 (50%; Figure 1). Losses were scored at 1p36 (75%) followed by 19p13 and 22q (67%), and 9q22, 9q34, 12q23-24, 17p12-13, 17q21, 19q13, and 21q22 (58%). The clear-cell carcinomas (n = 5 tumors with imbalances) showed frequent gains from 1q23-32, 2p24, 2p21, 2q14-22, 5p13-15, 7p14-21, 8q12-24, and 10q21-22 (80%) followed by 1q41-44, 2p22-23, 2p13, 2q12-13, 2q23-32, 3q13-24, 5q12-23, 5q32-34, 7p13, 7q21-34, 8q11, 10q11, 10q23-25, 12p11-13, 17q22-23, 19q13, 20q, and 22q11-12 (60%). Losses were most often scored at 4q21, 6p21, and 13q21 (80%) followed by 4q22-31, 6p22, 6q25-26, 13q12-14, 13q22-32, and 16p13 (60%; Figure 1). The mucinous carcinomas (n = 3 with imbalances) showed frequent gains of 7q22-31, 7q34, and 8q23 (67%). Losses were scored at 19p13, 19q13, and 22q11-12 in all three tumors with imbalances (100%) followed by losses of 7q11, 11q13, 12q24, 17p12-13, and 22q13 (67%; Figure 1). The low-grade serous carcinomas (n = 3 with imbalances) had gains mostly of 1q24, 7p13-21, and 7q21-35 (67%), while losses were commonly detected at 11q13, 17p12-13, 17q12-21, 22q12-13, and Xq12-13 (67%; Figure 1). Amplifications most frequently involved chromosomal bands 3q26 (12 tumors) followed by 8q23 (11 tumors), 8q22 (ten tumors), 8q24 (eight tumors), and 3q25 and 8q21 (seven tumors). The high-grade serous carcinomas showed amplifications in 3q26 in ten samples followed by 8q23 (n = 9), 8q22 (n = 8), 8q24 (n = 7), and 3q25 and 8q21 in six samples each. Four endometrioid carcinomas showed amplification, case 84 (Additional file 1: Table S1) in 3q26 and 12p, case 85 in 1q42-44, case 90 in 5p14, and case 93 in 3q25-29 and 6p21-22. Two clear-cell carcinomas showed amplifications: case 97 in 8q and case 100 in 8q13-21 and 8q22-23. The only low-grade serous carcinoma showing amplification (case 75) had it in 1q31, the undifferentiated carcinoma (case 110) showed amplification in 12q13, and a mucinous carcinoma (case 104) had 7q31 amplified.
Both tumors that had received (n = 15) and those that had not received (n = 41) neo-adjuvant therapy prior to the operation showed frequent gains from 3q and 7q; however, the neo-adjuvant group also showed gain of 11q14-22 in 27% of the abnormal cases, whereas the group that did not receive such treatment showed common additional gains from 1q, 2q, 8q, and 12p. Losses were often seen at 8p, 9q, and 10q in the neo-adjuvant subgroup but more commonly at 3p, 5q, 6q, 17p, 17q, and 22q in the normal group.
The average number of copy aberrations (ANCA) index was 39.7 for the high-grade serous carcinomas, 14.7 for the low-grade serous carcinomas, 33.7 for the endometrioid carcinomas, 35.2 for the clear-cell carcinomas, and 20.3 for the mucinous carcinomas. The ANCA index for the tumors (all subtypes taken together) that had received neoadjuvant treatment was 30.85 whereas the value for the group of tumors without neoadjuvant treatment was 39.01.