CLONAL ANALYAIA OF HUMAN NEOPLASIA

一种分析人类细胞克隆起源的有力新策略 种群已经发展起来了。这一策略涉及使用 同时检测限制性片段的重组DNA探针 X染色体基因长度多态和甲基化模式。我们的 长期目标是使用这一策略来研究特定的中心问题 在肿瘤和易发生肿瘤的X连锁疾病中。这个 近期目标是继续进行以下方面的研究： I.从活性基因中克隆分析附加基因的扩展 将克隆X染色体以增加多态标记的数量 可用于克隆分析。这将允许研究 几乎所有的女性。 二、具体疾病分析 1.结肠肿瘤。结肠腺瘤和结肠癌的克隆性起源 将被定义为确定这些肿瘤是否源自 或许多前体细胞。 2.膀胱移行细胞癌。调查将会是 进行检查以确定是否在 患有这种疾病的患者源于一次转化事件 随后的囊泡内扩散或多重独立转换 事件。 3.白血病。我们的研究表明，急性非淋巴细胞白血病 在活动性疾病期间，细胞分化形成成熟的粒细胞 在缓解期。建议进行研究，以确定这种情况的发生率 区分，确定特定的基因变化是否兼容 与分化，并阐明能力之间的相关性 鉴别和各种临床参数。 4.易发生肿瘤的X连锁疾病。克隆分析具有 识别某些X连锁疾病女性携带者的能力 与肿瘤有关。使用这种分析的可行性 为患有这些疾病的家庭提供遗传咨询将是 探索过了。

A powerful new strategy for analyzing the clonal origin of human cell populations has been developed. This strategy involves the use of recombinant DNA probes that simultaneously detect restriction fragment length polymorphisms and methylation patterns of X-chromosome genes. Our long term goals are to use this strategy to study specific central issues in neoplasia and X-linked diseases predisposing to neoplasia. The immediate goals are to continue our studies in the following areas: I. EXTENSIONOF CLONAL ANALYSIS Additional genes from the active X-chromosome will be cloned to increase the number of polymorphic markers that can be used for clonal analysis. This will allow the study of virtually any female. II. ANALYSIS OF SPECIFIC DISEASES 1. Colonic neoplasms. The clonal origin of colonic adenomas and carcinomas will be defined to determine whether these neoplasms are derived from one or many precursor cells. 2. Transitional cell carcinomas of the bladder. Investigations will be performed to determine whether the multiple bladder lesions found in patients with this disease are derived from one transformation event with subsequent intravesicular spread or multiple independent transformation events. 3. Leukemias. Our studies have shown that acute nonlymphocytic leukemia cells differentiate to form mature granulocytes both during active disease and during remission. Studies are proposed to define the incidence of this differentiation, determine whether specific genetic changes are compatible with differentiation, and elucidate correlations between the capacity to differentiate and various clinical parameters. 4. X-linked diseases predisposing to neoplasia. Clonal analysis has the capacity to identify female carriers of certain X-linked diseases associated with neoplasia. The feasibility of using such analyses to provide genetic counselling to families with these diseases will be explored.