Mutational analysis of the p15 and p16 genes in acute leukaemias.
Recently the p16 and related p15 genes have been described as candidate tumour suppressors at chromosome 9p21. These genes have been found to be homozygously deleted at a high frequency in several types of solid tumours and also in acute lymphoid leukaemias. In order to determine whether these genes are more widely involved in haematological malignancies, we have investigated a total of 84 samples that did not have homozygous p16 or p15 deletions from patients with acute lymphoid leukaemia (n=13), acute myeloid leukaemia (n=24) and chronic myeloid leukaemia in blast crisis (n=43) as well as four haemopoietic cell lines. p15 and p16 exon 1 and exon 2 were amplified by polymerase chain reaction (PCR), analysed by single-stranded conformation polymorphism (SSCP) and subsequently by sequencing. Within the p16 gene, a G-->A polymorphism at nucleotide 436 was found in 3/80 (4%) leukaemias and the cell line HL60. This cell line had also a C-->T mutation at nucleotide 232 which causes a premature stop codon. Analysis of the p15 gene revealed a C-->A mutation within the noncoding sequence 27 nucleotides upstream of exon 2 in 10/80 (13%) cases. These data show that inactivation of either the p15 or p16 gene by point mutation is a very uncommon event in acute leukaemias.
Sill
H
H
LRF Centre for Adult Leukaemia, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Aguiar
R C
RC
Schmidt
H
H
Hochhaus
A
A
Goldman
J M
JM
Cross
N C
NC
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors; D005091:Exons; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006412:Hematopoietic Stem Cells; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D047428:Protein Kinase Inhibitors; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins