P53 mutations in hairy cell leukemia

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.