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Analysis of p53 mutations in a large series of lymphoid hematologic
malignancies of childhood
M Wada, CR Bartram, H Nakamura, M Hachiya, DL Chen, J Borenstein, CW Miller, L Ludwig, TE Hansen-Hagge and WD Ludwig
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of
Medicine 90048.
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.
Volume 82,
Issue 10,
pp. 3163-3169,
11/15/1993
Copyright © 1993 by The American Society of Hematology
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