BIOCHEMICAL AND CYTOGENETIC MARKERS IN RETINOBLASTOMA

真正的基因对两者的发育负责 视网膜母细胞瘤(RB)和骨肉瘤最近被克隆 在我们的项目中。使用Rb基因的cDNA探针， 观察到结构变化(删除和重排) 在接受检查的40例视网膜母细胞瘤中，有16例 骨肉瘤。不管有没有发现结构像差， 视网膜母细胞瘤和骨肉瘤要么缺乏 RB成绩单或异常成绩单。 克隆了Rb基因，并证明它是丢失或 导致Rb基因的两个等位基因失活 视网膜母细胞瘤和骨肉瘤，我们的计划包括确定 在哪些其他癌症中，Rb基因在致病因素中起作用 肿瘤。主要候选对象包括：1.其他发生在 遗传性视网膜母细胞瘤患者，尤其是软组织 肉瘤，2.泡状横纹肌肉瘤，3.遗传性乳房 癌症，4.肺小细胞癌，5.黑色素瘤。 我们将检测上述肿瘤中的Rb基因，如下 以及其他肿瘤类型，以确定在 结构或RNA水平可以以类似的方式识别 视网膜母细胞瘤和骨肉瘤。幸运的是，我们小组有 获取一组独特的肿瘤标本，包括 世界上第二大恶性肿瘤病例最多 曾患过视网膜母细胞瘤的患者。这些研究可能已经 对理解的基础有极其重要的意义 人类癌症和在识别其他几种恶性肿瘤方面 其中Rb基因起着关键作用。 我们还将检查Rb基因是否具有致病作用 在其他以继承为主的家庭中 罹患癌症的倾向。最后，我们将检查所有 已知的癌基因在视网膜母细胞瘤中的表达， 骨肉瘤和其他Rb基因是 致病因素。 将使用的方法包括标准分子生物学 以及我们实验室目前可用的细胞遗传学技术。

The authentic gene responsible for the development of both retinoblastoma (Rb) and osteosarcoma has recently been cloned within our program. Using cDNA probes of the Rb gene, structural changes (deletions and rearrangements) were observed in 16 of 40 retinoblastomas examined as well as in an osteosarcoma. Whether or not structural aberrations were found, the retinoblastomas and osteosarcomas has either an absence of the Rb transcript or an abnormal transcript. Having cloned the Rb gene and shown that it is the loss or inactivation of both alleles of the Rb gene that is responsible for retinoblastoma and osteosarcoma, our plans include determining in which other cancers the Rb gene has a role in the etiology of the tumor. Prime candidates include: 1. other tumors arising in patients with hereditary retinoblastoma, especially soft tissue sarcomas, 2. alveolar rhabdomyosarcomas, 3. hereditary breast cancer, 4. small cell carcinoma of the lung and 5. melanomas. We shall examine the Rb gene in the tumors mentioned above as well as other tumor types to determine if changes at the structural or RNA level can be identified in a similar manner as retinoblastoma and osteosarcoma. Our group fortunately has access to a unique population of tumor specimens including the largest number of cases with second malignancies in the world who have previously had retinoblastoma. These studies could have extremely important implications in understanding the basis of human cancer and in identifying several other malignancies in which the Rb gene has a key role. We shall also examine whether the Rb gene has an etiological role in additional families who have dominantly inherited predisposition to develop cancer. Finally, we shall examine all known oncogenes for their expression in retinoblastomas, osteosarcomas, and other tumor in which the Rb gene is a causative factor. Methodologies to be used include standard molecular biological and cytogenetic techniques presently available in our laboratory.