Cytogenetic findings in 111 ovarian cancer patients: therapy-related chromosome aberrations and heterochromatic variants.
The chromosomes of 111 ovarian cancer patients were studied in G- and C-banded slides from peripheral blood lymphocyte (PBL) cultures for chromosome damage caused by chemotherapy and radiotherapy and for asymmetry of the constitutive heterochromatin of chromosomes 1, 9, and 16. We also monitored the survival of these patients to determine whether any secondary neoplasia induced by the therapy and report the findings of our investigations. Melphalan (MEL) was the only drug used in single-drug chemotherapy. The incidence of chromosome abnormalities in melphalan-treated cells (25%) was higher than in the control group (17%). The incidence of structural changes was also higher (10.5%) in the MEL-treated group than in controls (6%). After treatments with combinations of drugs, the incidence of structural changes remained at the same level (11%). In the patients receiving combined treatment with MEL and radiation, the rate of structural changes increased dramatically (24%). The overall rate of chromosome aberrations in this group was also higher (50%). Combination of two or more drugs and radiation produced only 14% structural chromosome changes. The overall rate of chromosome aberrations was also low (20%) in this group. Of 111 patients studied, only 33 were alive 6 years after initiation of the study. Of the surviving patients, eight had rearranged chromosomes in the first analysis. After 5 years, new blood samples were collected from these patients and chromosome analyses showed abnormal karyotypes in all eight patients. All chromosome abnormalities in the second analysis were completely unrelated to those in the first analysis, however. Whether the chromosome changes in the second analysis were due to therapy or to other unknown factors could not be determined. Data on C-banding and the distribution of inversions indicated that 91% of the patients had C-band heteromorphisms of chromosomes 1, 91% had heteromorphisms of chromosome 9, and 69% had heteromorphisms of chromosome 16. Furthermore, inversions were observed in chromosome 1 (41% of patients), chromosome 9 (28% of patients), and chromosome 16 (5% of patients).
Islam
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Department of Genetics, University of Gothenburg, Sweden.
Köpf
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Levan
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Granberg
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Friberg
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Levan
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002648:Child; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000187:drug effects / Q000528:radiation effects; D002899:Chromosomes, Human, Pair 9 / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D005500:Follow-Up Studies; D006570:Heterochromatin / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D007621:Karyotyping; D008558:Melphalan / Q000009:adverse effects; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D008937:Mitomycins / Q000009:adverse effects; D016609:Neoplasms, Second Primary / Q000209:etiology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D011878:Radiotherapy / Q000009:adverse effects*; D014178:Translocation, Genetic; D014750:Vincristine / Q000009:adverse effects
D000970:Antineoplastic Agents; D006570:Heterochromatin; D008937:Mitomycins; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D008558:Melphalan; D005472:Fluorouracil; D008727:Methotrexate