Clonal heterogeneity of p53 mutations in ovarian cancer.
We analyzed clonal populations of ovarian cancer cells for heterogeneity in p53 mutations (exons 4-9) and chemosensitivity. UL-3A cells were developed from a patient with stage IIIC ovarian adenocarcinoma. Heterogeneity in p53 mutations was demonstrated, ranging from point mutations to deletions in exons 4, 6 and 7. UL-3A cells contained two point mutations, in codon 248 of exon 7 and in codon 76 of exon 4. Five groups of clones were identified according to the p53 mutations. UL-3A clones with low p53 levels were more sensitive to CDDP (LD50 <8.0 microg/ml). Heterogeneity of p53 mutations may provide growth advantage during disease progression or chemotherapy.
Manahan
K J
KJ
University of Michigan School of Medicine, Ann Arbor, MI, USA.
Taylor
D D
DD
Gerçel-Taylor
C
C
D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D002999:Clone Cells; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D015151:Immunoblotting; D007928:Lethal Dose 50; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019772:Topotecan / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019772:Topotecan; D017239:Paclitaxel; D002945:Cisplatin