Gao X, Chen Y Q, Wu N, Grignon D J, Sakr W, Porter A T, Honn K V
Department of Radiation Oncology [Cancer Biology Division], Wayne State University School of Medicine, Detroit, Michigan 48202, USA.
Oncogene. 1995 Oct 5;11(7):1395-8.
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.
WAF1/CIP1基因是一种潜在的肿瘤抑制基因，最近已被克隆，并被确定为p53介质和G1细胞周期蛋白依赖性激酶（CDK）的抑制剂。我们进行这项研究以调查WAF1/CIP1基因在人类前列腺癌中的可能作用。通过巢式逆转录聚合酶链反应/单链构象多态性（RT-PCR/SSCP）和DNA测序，对18例前列腺癌患者的配对正常组织和癌组织进行WAF1/CIP1突变筛查。在三个肿瘤标本中观察到条带迁移，但配对的正常标本中未观察到。随后对PCR片段进行直接DNA测序，确定了四个序列改变，包括一个胞嘧啶（C）到腺嘌呤（A）的颠换、一个鸟嘌呤（G）到A的转换以及两个A插入。我们的结果表明，WAF1/CIP1基因发生突变，并且在人类前列腺癌的发病机制中可能很重要。这是原发性人类癌症中WAF1/CIP1突变的首次报道。
