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Tumor spreading to the contralateral ovary in bilateral ovarian carcinoma is a late event in clonal evolution.

Micci F, Haugom L, Ahlquist T, Abeler VM, Trope CG, Lothe RA, Heim S - J Oncol (2009)

Bottom Line: This was confirmed by the large number of similar changes detected by HR-CGH in the different lesions from the same patient.The chromosomal bands most frequently involved in structural rearrangements were 19p13 (n = 12) and 19q13 (n = 11).The chromosomal bands most frequently gained by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12 (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, 0310 Oslo, Norway.

ABSTRACT
Cancer of the ovary is bilateral in 25%. Cytogenetic analysis could determine whether the disease in bilateral cases is metastatic or two separately occurring primary tumors, but karyotypic information comparing the two cancerous ovaries is limited to a single report with 11 informative cases. We present a series of 32 bilateral ovarian carcinoma cases, analyzed by karyotyping and high-resolution CGH. Our karyotypic findings showed that spreading to the contralateral ovary had occurred in bilateral ovarian cancer cases and that it was a late event in the clonal evolution of the tumors. This was confirmed by the large number of similar changes detected by HR-CGH in the different lesions from the same patient. The chromosomal bands most frequently involved in structural rearrangements were 19p13 (n = 12) and 19q13 (n = 11). The chromosomal bands most frequently gained by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12 (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%). This is the first time that 5p14 is seen gained at such a high frequency in cancer of the ovary; possibly oncogene(s) involved in bilateral ovarian carcinogenesis or tumor progression may reside in this band.

No MeSH data available.


Related in: MedlinePlus

(a) All genomic imbalances detected by HR-CGH in 56 tumor lesions from altogether 32 cases of bilateral ovarian cancer (including six metastases to the omentum/peritoneum). (b) Genomic imbalances detected by HR-CGH in both tumorous ovaries from the 23 cases yielding informative results. The data from the latter subset are likely to reflect the earliest genomic changes, since they are present in both tumor lesions. Some of the imbalances in the former and larger group may have been acquired after spreading, since they also include findings in only one tumor per case.
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Related In: Results  -  Collection


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fig3: (a) All genomic imbalances detected by HR-CGH in 56 tumor lesions from altogether 32 cases of bilateral ovarian cancer (including six metastases to the omentum/peritoneum). (b) Genomic imbalances detected by HR-CGH in both tumorous ovaries from the 23 cases yielding informative results. The data from the latter subset are likely to reflect the earliest genomic changes, since they are present in both tumor lesions. Some of the imbalances in the former and larger group may have been acquired after spreading, since they also include findings in only one tumor per case.

Mentions: The HR-CGH gave informative results on 60 samples showing genomic imbalances in 56 of them. From seven lesions there was no DNA available for analysis. No informative results were obtained in cases 13b, 22b, and 32b because of poor quality of the hybridization signal, despite running the experiments twice. In six cases, the G-banding karyotype matched the imbalances detected by CGH well. However, because the G-banding analysis often showed an incomplete karyotype with marker chromosomes and additional material of unknown origin sitting on known chromosomes, the CGH analysis allowed the identification of more imbalances. In 17 cases, a normal karyotype was detected by G-banding analysis whereas the CGH experiments showed genomic imbalances in the tumor samples. We gained information also on the 10 cases that were culture failures, finding imbalances in seven of them. Gains were more frequent than losses as seen by HR-CGH, and high-level amplification was found in 23 lesions. The major copy number changes were gains of or from chromosome arms 1p, 1q, 2p, 3q, 5p, 8q, 11q, 12p, and 20q and losses of or from Xp, 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 18q, 19q, and 22q. More specifically, the most frequently gained bands were, in order of decreasing frequency, 5p14 and 8q23 (39%), 2p23 (38%), 1q24, 3q25, and 3q27q28 (36%), 1q21, and 3q22 (34%), 2p13, 3q13, and 8q21 (32%), 1p31 (30%), 20q13 (29%), and 11q22 and 12p12 (25%). The most frequently lost bands were 17p11 and 17p13 (45%), 17p12 (43%), 16q23 and 22q13 (38%), 8p21 and 17q21 (34%), 8p22-23 (32%), Xp21 and 6q25 (30%), 4q34, and 18q22 (29%), 13q14 and 19q13 (27%), and 5q13-14 (25%) (Figure 3(a)). A comparison of the imbalances scored for the tumors in the two ovaries and/or the omentum/peritoneum showed that the bands most often gained by both ovarian tumors were 5p14 (70% of the 23 cases or 46 samples showing informative results), 8q23-24 (65%), 1q23-24 (57%), 12p12 (48%), 2q23 and 3q22 (43%), and 2p23, 3q13-21, 3q24-28, and 11q14 (39%). The most often lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), 8p22-23 (48%), 16q22-23, 17q12-21, and 18q22 (43%), and 4q31, 4q33q34, 11p15, and Xp21 (39% each; Figure 3(b)).


Tumor spreading to the contralateral ovary in bilateral ovarian carcinoma is a late event in clonal evolution.

Micci F, Haugom L, Ahlquist T, Abeler VM, Trope CG, Lothe RA, Heim S - J Oncol (2009)

(a) All genomic imbalances detected by HR-CGH in 56 tumor lesions from altogether 32 cases of bilateral ovarian cancer (including six metastases to the omentum/peritoneum). (b) Genomic imbalances detected by HR-CGH in both tumorous ovaries from the 23 cases yielding informative results. The data from the latter subset are likely to reflect the earliest genomic changes, since they are present in both tumor lesions. Some of the imbalances in the former and larger group may have been acquired after spreading, since they also include findings in only one tumor per case.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2744120&req=5

fig3: (a) All genomic imbalances detected by HR-CGH in 56 tumor lesions from altogether 32 cases of bilateral ovarian cancer (including six metastases to the omentum/peritoneum). (b) Genomic imbalances detected by HR-CGH in both tumorous ovaries from the 23 cases yielding informative results. The data from the latter subset are likely to reflect the earliest genomic changes, since they are present in both tumor lesions. Some of the imbalances in the former and larger group may have been acquired after spreading, since they also include findings in only one tumor per case.
Mentions: The HR-CGH gave informative results on 60 samples showing genomic imbalances in 56 of them. From seven lesions there was no DNA available for analysis. No informative results were obtained in cases 13b, 22b, and 32b because of poor quality of the hybridization signal, despite running the experiments twice. In six cases, the G-banding karyotype matched the imbalances detected by CGH well. However, because the G-banding analysis often showed an incomplete karyotype with marker chromosomes and additional material of unknown origin sitting on known chromosomes, the CGH analysis allowed the identification of more imbalances. In 17 cases, a normal karyotype was detected by G-banding analysis whereas the CGH experiments showed genomic imbalances in the tumor samples. We gained information also on the 10 cases that were culture failures, finding imbalances in seven of them. Gains were more frequent than losses as seen by HR-CGH, and high-level amplification was found in 23 lesions. The major copy number changes were gains of or from chromosome arms 1p, 1q, 2p, 3q, 5p, 8q, 11q, 12p, and 20q and losses of or from Xp, 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 18q, 19q, and 22q. More specifically, the most frequently gained bands were, in order of decreasing frequency, 5p14 and 8q23 (39%), 2p23 (38%), 1q24, 3q25, and 3q27q28 (36%), 1q21, and 3q22 (34%), 2p13, 3q13, and 8q21 (32%), 1p31 (30%), 20q13 (29%), and 11q22 and 12p12 (25%). The most frequently lost bands were 17p11 and 17p13 (45%), 17p12 (43%), 16q23 and 22q13 (38%), 8p21 and 17q21 (34%), 8p22-23 (32%), Xp21 and 6q25 (30%), 4q34, and 18q22 (29%), 13q14 and 19q13 (27%), and 5q13-14 (25%) (Figure 3(a)). A comparison of the imbalances scored for the tumors in the two ovaries and/or the omentum/peritoneum showed that the bands most often gained by both ovarian tumors were 5p14 (70% of the 23 cases or 46 samples showing informative results), 8q23-24 (65%), 1q23-24 (57%), 12p12 (48%), 2q23 and 3q22 (43%), and 2p23, 3q13-21, 3q24-28, and 11q14 (39%). The most often lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), 8p22-23 (48%), 16q22-23, 17q12-21, and 18q22 (43%), and 4q31, 4q33q34, 11p15, and Xp21 (39% each; Figure 3(b)).

Bottom Line: This was confirmed by the large number of similar changes detected by HR-CGH in the different lesions from the same patient.The chromosomal bands most frequently involved in structural rearrangements were 19p13 (n = 12) and 19q13 (n = 11).The chromosomal bands most frequently gained by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12 (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, 0310 Oslo, Norway.

ABSTRACT
Cancer of the ovary is bilateral in 25%. Cytogenetic analysis could determine whether the disease in bilateral cases is metastatic or two separately occurring primary tumors, but karyotypic information comparing the two cancerous ovaries is limited to a single report with 11 informative cases. We present a series of 32 bilateral ovarian carcinoma cases, analyzed by karyotyping and high-resolution CGH. Our karyotypic findings showed that spreading to the contralateral ovary had occurred in bilateral ovarian cancer cases and that it was a late event in the clonal evolution of the tumors. This was confirmed by the large number of similar changes detected by HR-CGH in the different lesions from the same patient. The chromosomal bands most frequently involved in structural rearrangements were 19p13 (n = 12) and 19q13 (n = 11). The chromosomal bands most frequently gained by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12 (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%). This is the first time that 5p14 is seen gained at such a high frequency in cancer of the ovary; possibly oncogene(s) involved in bilateral ovarian carcinogenesis or tumor progression may reside in this band.

No MeSH data available.


Related in: MedlinePlus