p53 mutations and microsatellite instability in ovarian cancer: Yin and Yang
p53 mutations and microsatellite instability in ovarian cancer: Yin and Yang
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DOI：
10.1067/mob.2001.113856
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发表时间：
2001-04-01
影响因子：
9.8
通讯作者：
Sood, AK
中科院分区：
文献类型：
--
作者：
Buller, RE;Shahin, MS;Sood, AK
目的：我们测试了卵巢癌中 p53 移码突变是由于基因组不稳定而不是该过程的直接原因而发生的假设。 研究设计：已对 305 例卵巢癌、输卵管癌和腹膜癌进行了 p53 肿瘤抑制基因的测序。鉴定出两组 p53 无效突变：(1) 由移码插入或缺失突变引起的突变 (n = 31) 和 (2) 由无义突变引起的突变 (n = 28)。作为对照组，根据诊断时患者年龄、癌症分期和分级、癌症部位和诊断年份，通过与 p53 缺失肿瘤匹配，选择 59 个具有 p53 错义突变的肿瘤。通过以下不同标记物从配对的正常和肿瘤组织脱氧核糖核酸测定微卫星不稳定性：D2S123、D5S346、D17S250、BAT25和BAT26。在 7% 聚丙烯酰胺凝胶上评估来自聚合酶链反应的放大器。结果：p53 缺失肿瘤更有可能处于较高阶段和级别。 p53 移码组中输卵管癌更为常见 (P = 0.02)。对于具有 p53 移码无义突变和错义突变的肿瘤，微卫星不稳定的总体发生率分别为 39%、36% 和 25% (P =.30)。微卫星不稳定几乎只见于卵巢癌（P=.04）。结论：微卫星不稳定是卵巢癌中相对常见的事件，并且取决于标记物的选择。 p53 移码突变似乎并不是基因组不稳定的结果。
OBJECTIVE: We tested the hypothesis that p53 frameshift mutations in ovarian cancer occur as a result of genomic instability rather than as a proximal cause of this process.STUDY DESIGN: Sequencing of the p53 tumor suppressor gene has been carried out on 305 ovarian, fallopian tube, and peritoneal cancers. Two groups of p53 null mutations were identified: (1) those caused by frameshift insertion or deletion mutations (n = 31) and (2) those caused by nonsense mutations (n = 28). As a control group 59 tumors with p53 missense mutations were selected by matching with the p53 null tumors on the basis of patient age at diagnosis, stage and grade of cancer, cancer site, and year of diagnosis. Microsatellite instability was determined from paired normal and tumor tissue deoxyribonucleic acid by means of the following different markers: D2S123, D5S346, D17S250, BAT25, and BAT26. Amplimers from polymerase chain reactions were evaluated on 7% polyacrylamide gels.RESULTS: The p53 null tumors were more likely to be of higher stage and grade. Fallopian tube cancers were more common (P =.02) in the p53 frameshift group. The overall incidence of microsatellite instability was 39%, 36%, and 25% for tumors with p53 frameshift nonsense and missense mutations (P =.30). Microsatellite instability was seen almost exclusively with ovarian cancer (P=.04).CONCLUSIONS: Microsatellite instability is a relatively common event in ovarian cancer and is dependent on marker selection. The p53 frameshift mutations do not appear to occur as a consequence of genomic instability.