CLONAL ANALYSIS OF HUMAN NEOPLASIA

一种分析人类细胞克隆起源的新策略 人口得到了发展。 该战略涉及使用 同时检测限制性片段的重组DNA探针 X染色体基因的长度多态性和甲基化模式。 我们 长期目标是利用这一战略来研究具体的中心问题 在肿瘤和易诱发肿瘤的X连锁疾病中。 的 近期目标是继续在以下领域进行研究： I. 克隆分析的扩展来自活性表达载体的额外基因 X染色体将被克隆以增加多态性标记的数量 可用于克隆分析。 这将有助于研究 几乎所有的女性。 二.特定疾病分析 1.结肠肿瘤。 结肠腺瘤和癌的克隆起源 将被定义，以确定这些肿瘤是否来自一个 或许多前体细胞。 2.膀胱移行细胞癌。 调查将 进行，以确定是否发现多个膀胱病变， 患有这种疾病的患者来自一个转化事件， 随后囊内扩散或多次独立转化 事件 3.白血病 我们的研究表明急性非淋巴细胞白血病 细胞分化形成成熟的粒细胞， 在缓解期间。 建议进行研究来定义这种情况的发生率 分化，确定特定的遗传变化是否兼容 与分化，并阐明能力之间的相关性， 区分和各种临床参数。 4.易发生肿瘤的X连锁疾病。 克隆分析具有 确定某些X连锁疾病女性携带者的能力 与肿瘤有关。 利用这种分析来 为患有这些疾病的家庭提供遗传咨询， 探讨了

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.