Mutations of the P53 gene in acute myeloid leukaemia.
In a previous report we found point mutations in exons 5-8 of the P53 gene in five of 46 patients with acute myeloid leukaemia (AML), with a predominance of mutations in the 10 patients with 17p monosomy. In this report we extended our findings studying such mutations in 66 unselected additional cases of AML, using polymerase chain reaction single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing. Three of the 66 new cases had a point mutation, leading to a change in one encoded amino acid. Thus, eight of the 112 AML studied had P53 mutations in exons 5-8, suggesting that the incidence of P53 mutation is relatively low in AML. A predominance of mutations in exon 8 (5/8) was found. Six of the eight patients with mutations were older than 60 years of age, and all eight cases had a short survival. All seven mutated cases karyotyped showed complex cytogenetic findings, especially monosomy 5 and/or 7, thus questioning the pathogenic importance of P53 mutations in a context of multiple genetic abnormalities. However, five of them also had 17p monosomy, and in the remaining two cases SSCP and sequence analysis also suggested loss of the normal P53 allele. This supported a role for the P53 gene mutations in leukaemogenesis in the relatively small number of AML patients in whom they were found, through loss of tumour suppressive activity of both normal P53 alleles, as reported in solid tumours.
Fenaux
P
P
Service des Maladies du Sang, CHU, Lille, France.
Preudhomme
C
C
Quiquandon
I
I
Jonveaux
P
P
Laï
J L
JL
Vanrumbeke
M
M
Loucheux-Lefebvre
M H
MH
Bauters
F
F
Berger
R
R
Kerckaert
J P
JP
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence / Q000235:genetics; D002648:Child; D004273:DNA, Neoplasm / Q000737:chemistry; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm