title: Cytogenetic observations of a human ovarian carcinoma clinically resistant to therapy.
abstract: Resistance of a cancer cell to therapy represents an important problem in tumor biology. Hypotheses concerning the mechanism of resistance have included genetic instability, gene amplification, aneuploidy, and altered cell growth kinetics. Cytogenetic assays allow for the analysis of each of these parameters and provide important information concerning tumor heterogeneity. In using cytogenetic analysis, we have analyzed a human ovarian carcinoma clinically resistant to therapy. The ovarian carcinoma had a complex but stable karyotype with a mean chromosome number of 61.7 chromosomes/cell. Approximately 50% of the metaphase preparations examined had double-minute chromosomes, which have sometimes been associated with gene amplification. The frequency of double minutes varied from one pair to hundreds of pairs per cell. Cell cycle kinetic analysis revealed an average generation time of 38 hours. The cells were relatively resistant to doxorubicin in vitro, and the baseline sister chromatid exchange frequency, a measure of genetic instability, was elevated. These results suggest that cytogenetic assays have potential as predictive assays of tumor chemoresistance and may provide information regarding the biologic aggressiveness encountered clinically.
authors.affiliation: Department of Obstetrics and Gynecology, Pritzker School of Medicine, University of Chicago, IL 60637.
authors.forename: J
authors.initials: J
authors.lastname: Rotmensch
authors.forename: T E
authors.initials: TE
authors.lastname: Turkula
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
authors.forename: J L
authors.initials: JL
authors.lastname: Schwartz
mesh_terms: D002453:Cell Cycle; D002874:Chromosome Mapping; D003536:Cystadenocarcinoma / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D003582:Cytogenetics; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007621:Karyotyping; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D012854:Sister Chromatid Exchange
chemical_list: D004317:Doxorubicin