Tsao S W, Mok C H, Oike K, Muto M, Goodman H M, Sheets E E, Berkowitz R S, Knapp R C, Lau C C
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115.
Anticancer Res. 1991 Nov-Dec;11(6):1975-82.
Previous reports have shown that one copy of the chromosome 17 was frequently lost in human ovarian cancers (1). The position of the allelic deletion has not been mapped and involvement of p53 gene has not been determined. In this study, we have shown that in human ovarian carcinoma, the commonest region of allelic loss in chromosome 17p is 17p 13.3 (65%) and 17p13.1 (63.7%; 6 out of 9 informative cases). Allelic loss was also observed at region 17p12 - 11.1 but at a lower frequency (38.6% to 37.5%). The pattern of allelic loss of p53 gene was consistent in both primary and secondary metastatic tumors of the same patient. No gross rearrangement of p53 was however observed at the remaining allele using Southern blot analysis. Allelic loss of p53 gene was closely associated with 17p 13.3, the terminal portion of chromosome 17p. The high frequency of allelic loss of p53 gene in ovarian carcinomas conformed with recent findings in cancers of colon, breast, lung and brain suggesting inactivation of p53 gene play a rate limiting step in pathogenesis of human malignancies.
以往的报告显示,在人类卵巢癌中,17号染色体的一个拷贝经常缺失(1)。等位基因缺失的位置尚未定位,p53基因的参与情况也未确定。在本研究中,我们发现,在人类卵巢癌中,17号染色体短臂上等位基因缺失最常见的区域是17p13.3(65%)和17p13.1(63.7%;9例信息充分的病例中有6例)。在17p12 - 11.1区域也观察到等位基因缺失,但频率较低(38.6%至37.5%)。同一患者的原发性和继发性转移瘤中p53基因的等位基因缺失模式是一致的。然而,使用Southern印迹分析在其余等位基因上未观察到p53的明显重排。p53基因的等位基因缺失与17号染色体短臂的末端部分17p13.3密切相关。卵巢癌中p53基因等位基因缺失的高频率与结肠癌、乳腺癌、肺癌和脑癌的最新发现一致,表明p53基因的失活在人类恶性肿瘤的发病机制中起限速作用。