THE MOLECULAR GENETICS OF GYNECOLOGIC CANCERS

妇科癌症仍然是这个地区女性的主要健康问题。 每年约有25,000人死于此病 有问题。不幸的是，大多数这些肿瘤在以下情况下仍无法治愈 确诊时已进入晚期。这个项目的目的是 描述这组肿瘤的分子遗传学，并最终 将这些信息用于临床应用，合理设计 治疗、早期发现和预防试验。 我们已经确定了横跨子宫内膜和卵巢的标本 从良性到恶性的组织学谱中的突变 Ras、P53和Rb基因。对于子宫内膜癌，我们已经分析了 刮宫标本。激活的ras基因在非典型 增生症(14%)和子宫内膜癌(5%)；p53突变是 在大约15%的不典型增生和癌中发现。 这些研究将有助于识别分子遗传事件 子宫内膜癌的发生及其在ITS中的应用 及早发现。 对卵巢肿瘤的评估显示发现激活的ras基因。 在良性(10%)和“LMP”肿瘤(30%)中，而卵巢癌(5- 10%)不要。此外，肿瘤抑制基因p53的突变 和Rb出现在卵巢癌中(分别为48%和14%)，但 在LMP肿瘤中不存在。这表明这些肿瘤是离散的。 生物实体。我们现在通过检查143个来扩展这些结果 来自一项大型前瞻性试验的晚期卵巢癌标本 (GOG#111)以了解P53基因突变和P53基因过表达 HER2/neu。未来的项目将研究p53突变的价值，如 卵巢癌预后或早期检测标记物 检查大量早期卵巢癌。这将是 包括从GOG#95为 HER2/neu、P53、EGFR的表达 最后，确定潜在的卵巢癌新标记物和基因 恶性卵巢上皮在其发病机制中具有重要作用 与使用差异显示技术的良性对应物进行比较。 差异表达的基因将被分离、克隆和 以其在卵巢癌发展中的作用为特征。

Gynecologic cancer remains a major health problem for women in this country, with approximately 25,000 deaths annually attributed to this problem. Unfortunately, most of these tumors remain untreatable when diagnosed in the advanced stage. The purpose of this project is to characterize the molecular genetics of this group of tumors and ultimately use that information for clinical application in rationally designing therapeutic, early detection, and prevention trials. We have characterized endometrial and ovarian specimens which span the histologic spectrum from benign to malignant for mutations in the ras, p53 and Rb genes. For endometrial cancers, we have analyzed curettage specimens. Activated ras genes are found in the atypical hyperplasias (14%) and endometrial carcinomas (5%); p53 mutations are found in approximately 15% of atypical hyperplasia and carcinomas. These studies will help to identify the molecular genetic events that are important in the genesis of endometrial cancer and their use for the its early detection. Evaluation of ovary tumors revealed that activated ras genes are found in benign (10%) and "LMP" tumors (30%) while ovarian carcinomas (5- 10%) do not. In addition, mutations in the tumor suppressor genes p53 and Rb occur in ovarian carcinomas (48 and 14% respectively) but are not present in LMP tumors. This suggested that these tumors are discrete biologic entities. We are now extending these results by examining 143 specimens of advanced ovarian cancer from a large prospective trial (GOG#111) for mutations in the p53 gene and overexpression of HER2/neu. Future projects will examine the value of p53 mutations as a prognostic or an early detection marker in ovarian cancers by examining large numbers of early stage ovarian cancers. This will involve characterizing early ovarian cancers from GOG#95 for the expression of HER2/neu, p53 and EGFR. Finally, to identify potential new markers of ovarian cancer and genes important in its pathogenesis, malignant ovarian epithelium is being compared to its benign counterpart using differential display technology. Genes which are differentially expressed will be isolated, cloned and characterized for their role in the development of ovarian cancer.