P53 mutations in hairy cell leukemia

• Published in: Leukemia Vol. 14; no. 4; pp. 706 - 711
• Main Authors: KÖNIG, E. A, KUSSER, W. C, DAY, C, PORZSOLT, F, GLICKMAN, B. W, MESSER, G, SCHMID, M, DE CHATEL, R, MARCSEK, Z. L, DEMETER, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.04.2000; Nature Publishing Group
• Subjects: Adult; Aged; Amino Acid Substitution; Biological and medical sciences; Cell Cycle; Codon; Cohort Studies; CpG Islands; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; DNA, Neoplasm - blood; DNA, Neoplasm - genetics; Female; Genes, p53; Hairy cell leukemia; Hematologic and hematopoietic diseases; Humans; Leukemia; Leukemia, Hairy Cell - genetics; Leukemia, Hairy Cell - mortality; Leukemia, Hairy Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Lymphoma, Non-Hodgkin - genetics; Lymphoma, Non-Hodgkin - mortality; Male; Medical sciences; Middle Aged; Mutation; Patients; Peripheral blood; Point Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Prognosis; Sequence Deletion; Spleen; Spleen - chemistry; Human; Chronic; Hairy cell leukemia; TP53 Gene; Lymphoproliferative syndrome; Exploration; Malignant hemopathy; Mutation; Molecular biology; Tumor suppressor gene
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2401721

We have studied the frequency of p53 mutations in genomic DNA extracted from peripheral blood or the spleen of 61 patients with hairy cell leukemia using PCR-SSCP and automated cycle sequencing. We identified exon 5-8 mutations in 17 cases, corresponding to a frequency of 28%. In four cases, mutations were localized in exon 5; one patient with atypical HCL had a mutation in exon 6 at the 3' boundary; five cases showed mutations in exon 7, while exon 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 at CpG dinucleotides. The rate of p53 mutations found in this large cohort of HCL patients is unexpectedly high as in other non-Hodgkin lymphomas p53 mutations predict for poor treatment outcome. The character of the mutations we have found is entirely different from that described in other hematologic malignancies.