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Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood

Item Type:Article
Title:Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood
Creators Name:Wada, M. and Bartram, C.R. and Nakamura, H. and Hachiya, M. and Chen, D.L. and Borenstein, J. and Miller, C.W. and Ludwig, L. and Hansen-Hagge, T.E. and Ludwig, W.D. and Reiter, A. and Mizoguchi, H. and Hoeffler, H.P.
Abstract:p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion.
Keywords:Base Sequence, p53 Genes, Leukemia, Lymphoma, Molecular Sequence Data, Mutation
Publisher:American Society of Hematology
Page Range:3163-3169
Date:15 November 1993
Official Publication:http://bloodjournal.hematologylibrary.org/cgi/content/abstract/82/10/3163
PubMed:View item in PubMed

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