p53 mutations in hairy cell leukemia.
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.
König
E A
EA
Department of Molecular Genetics, Semmelweis University, School of Medicine, Budapest, Hungary.
Kusser
W C
WC
Day
C
C
Porzsolt
F
F
Glickman
B W
BW
Messer
G
G
Schmid
M
M
de Châtel
R
R
Marcsek
Z L
ZL
Demeter
J
J
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002453:Cell Cycle; D003062:Codon; D015331:Cohort Studies; D018899:CpG Islands; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D016158:Genes, p53; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D017384:Sequence Deletion; D013154:Spleen / Q000737:chemistry
D003062:Codon; D004273:DNA, Neoplasm