We have studied the frequency of p53 mutations in genomic DNA extracted fro
m peripheral blood or the spleen of 61 patients with hairy cell leukemia us
ing PCR-SSCP and automated cycle sequencing. We identified exon 5-8 mutatio
ns in 17 cases, corresponding to a frequency of 28%. In four cases, mutatio
ns were localized in exon 5; one patient with atypical HCL had a mutation i
n exon 6 at the 3' boundary; five cases showed mutations in exon 7, while e
xon 8 was found to be mutated in seven cases. The mutations found could be
divided into three major categories: structural (n=9), inactivating (n=6),
and neutral (n=2) mutations. None of the three transitions found occurred a
t CpG dinucleotides. The rate of p53 mutations found in this large cohort o
f HCL patients is unexpectedly high as in other non-Hodgkin lymphomas p53 m
utations predict for poor treatment outcome. The character of the mutations
we have found is entirely different from that described in other hematolog
ic malignancies.