Journal article
p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer
Clinical cancer research, Vol.8(5), pp.973-985
05/2002
PMID: 12006509
Abstract
Although p53 mutations occur in alkylating agent-related leukemias, their frequency and spectrum in leukemias after ovarian cancer have not been addressed. The purpose of this study was to examine p53 mutations in leukemias after ovarian cancer, for which treatment with platinum analogues was widely used.
Adequate leukemic or dysplastic cells were available in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven of the 17 received platinum compounds and other alkylating agents with or without DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5, 6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by sequencing.
Eleven p53 mutations involving all four exons studied and one polymorphism were identified. Genomic DNA analyses were consistent with loss of heterozygosity for four of the mutations. The 11 mutations occurred in 9 cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6 leukemias after other treatments (50%) contained p53 mutations. Two leukemias that occurred after treatment with platinum analogues contained two mutations. Among eight mutations in leukemias after treatment with platinum analogues, there were four G-to-A transitions and one G-to-C transversion.
p53 mutations are common in leukemia and myelodysplastic syndrome after multiagent therapy for ovarian cancer. The propensity for G-to-A transitions may reflect specific DNA damage in leukemias after treatment with platinum analogues.
Details
- Title: Subtitle
- p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer
- Creators
- Debra G B Leonard - Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104, USALois B TravisKathakali AddyaGraca M DoresEric J HolowatyKjell BergfeldtDavid MalkinBetsy A KohlerCharles F LynchTom WiklundMarilyn StovallPer HallEero PukkalaDiana J SlaterCarolyn A Felix
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.8(5), pp.973-985
- Publisher
- United States
- PMID
- 12006509
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- CA77683 / NCI NIH HHS CA80175 / NCI NIH HHS CA85469 / NCI NIH HHS N01-CP-50134 / NCI NIH HHS
- Language
- English
- Date published
- 05/2002
- Academic Unit
- Epidemiology
- Record Identifier
- 9983995017302771
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