Somatic mutations of the WAF1/CIP1 gene in primary prostate cancer.
The WAF1/CIP1 gene, a potential tumor suppressor gene, has recently been cloned and identified as a p53 mediator and an inhibitor for G1 cyclin-dependent kinases (CDKs). We undertook this study to investigate the possible role of the WAF1/CIP1 gene in human prostatic carcinoma. Matched normal and cancer tissues from 18 patients with prostate cancer were screened for WAF1/CIP1 mutation by nested reverse transcription-polymerase chain reaction/single strand conformational polymorphism (RT-PCR/SSCP) and DNA sequencing. Shifted bands from three tumor, but not the matched normal specimens, were observed. Subsequent direct DNA sequencing of the PCR fragments identified four sequence alterations including a cytosine (C) to adenine (A) transversion and a guanine (G) to A transition and two A insertions. Our results demonstrated that mutations of the WAF1/CIP1 gene occur and may be important during the pathogenesis of human prostate cancer. This is the first report of WAF1/CIP1 mutation in a primary human cancer.
D001483:Base Sequence; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000235:genetics*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers