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人死于这些 癌症。这个项目的目的是描述分子的特征 这组肿瘤的遗传学，并最终利用这些信息 临床应用于设计治疗和预防试验。 我们已经确定了63个卵巢肿瘤的特征，这些肿瘤跨越了组织学范围 从良性囊腺瘤到“低恶性潜能”肿瘤 Ras、p53和Rb癌基因突变与卵巢癌的关系。 这项研究的结果显示，在10%的人中发现了激活的ras基因。 良性囊腺瘤和30%的LMP肿瘤，但不在卵巢 癌症。此外，肿瘤抑制基因p53和P53的突变 Rb发生在卵巢癌中(分别为48%和14%)，但不是 存在于LMP肿瘤中。这表明这些肿瘤是离散的。 生物实体。更有趣的是，激活的RAS的发生率 LMP肿瘤中的基因在更晚期的肿瘤中更高，这表明它是一种 这些肿瘤的预后不良因素。未来的项目将检查 P53基因突变作为肺癌预后或早期检测指标的价值 卵巢癌早期和晚期的大量检查 卵巢癌。 我们还检查了横跨组织学检查的子宫内膜标本 从良性到恶性的ras和p53基因突变谱。 在非典型增生中发现激活的ras基因(14%)和 子宫内膜癌(5%)。约15%的人发现罕见的p53突变 增生性疾病和癌症。这些研究将有助于确定 在这些疾病的发生中起重要作用的分子遗传事件 肿瘤。此外，它还将描述 这些事件使人们能够确定这些分子损伤中是否有任何 可作为早期疾病的标志。

Gynecologic cancers remains a major health problem for women in this country with approximately 25,000 deaths annually attributed to these cancers. 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 designing therapeutic and prevention trials. We have characterized 63 ovarian tumors which span the histologic spectrum from benign cystadenomas through tumors of "low malignant potential" to ovarian carcinomas for mutations in the ras , P53, and Rb oncogenes. Results from this study revealed that activated ras genes are found in 10% of benign cystadenomas and 30% of "LMP" tumors but not in ovarian carcinomas. 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. Of further interest, the incidence of activated ras genes in LMP tumors is higher in more advanced tumors suggesting it is a negative prognostic factor for these tumors. 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 and advanced stage ovarian cancers. We are also examining endometrial specimens which span the histologic spectrum from benign to malignant for mutations in the ras and p53 genes. Activated ras genes are found in the atypical hyperplasias (14%) and endometrial carcinomas (5%). P53 mutations rare found in approximately 15% of hyperplasia and carcinomas. These studies will help to identify the molecular genetic events which are important in the genesis of these tumors. In addition, it will characterize the temporal relationship among these events enabling one to determine if any of these molecular lesions can be used as markers of early disease.