Mutations of the p53 gene in B-cell chronic lymphocytic leukemia: a report on 39 cases with cytogenetic analysis.
Mutations of exons 5 to 8 of the p53 gene were looked for in 39 cases of B-cell chronic lymphocytic leukemia (CLL) using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing. All patients also had cytogenetic analysis. A point mutation, leading to an amino acid change in the p53 protein was found in four cases, involving exon 7 (one case) or exon 8 (three cases). Mutations seemed to predominate in advanced clinical stages (Binet's stage C). All four patients with 17p monosomy had a mutation whereas no mutation was found in the 35 patients with cytogenetically normal 17p. These findings suggest that p53 mutations are relatively rare in B-cell CLL, and largely predominate or may even be restricted to patients with 17p monosomy (who constitute about 5% of all B-cell CLL patients in large published series). In those patients, the mutations may play a role in leukemogenesis through loss of tumor suppressive activity of normal p53 genes.
Fenaux
P
P
Service des Maladies du Sang, CHU, Lille, France.
Preudhomme
C
C
Laï
J L
JL
Quiquandon
I
I
Jonveaux
P
P
Vanrumbeke
M
M
Sartiaux
C
C
Morel
P
P
Loucheux-Lefebvre
M H
MH
Bauters
F
F
D000368:Aged; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009006:Monosomy; D009154:Mutation; D009691:Nucleic Acid Denaturation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded