SOMATIC MUTATIONS OF THE WAF1 CIP1 GENE IN PRIMARY PROSTATE-CANCER/

The WAF1/CIP1 gene, a potential tumor suppressor gene, has recently be en cloned and identified as a p53 mediator and an inhibitor for G1 cyc lin-dependent kinases (CDKs). We undertook this study to investigate t he possible role of the WAF1/CIP1 gene in human prostatic carcinoma. M atched 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 (R T-PCR/SSCP) and DNA sequencing. Shifted bands from three tumor, but no t the matched normal specimens, were observed. Subsequent direct DNA s equencing of the PCR fragments identified four sequence alterations in cluding a cytosine (C) to adenine (A) transversion and a guanine (G) t o A transition and two A insertions. Our results demonstrated that mut ations of the WAF1/CTP1 gene occur and may be important during the pat hogenesis of human prostate cancer. This is the first report of WAF1/C IP1 mutation in a primary human cancer.