ISOLATION OF GENES FOR PAGET DISEASE AND OSTEOSARCOMA

描述（改编自申请人的摘要）： 骨是一种以异常破骨细胞为特征的常见骨疾病， 大，过度活跃，多核，并含有副粘病毒样核 内含物。 这是一种相对常见的疾病，估计发病率 在40岁以上的人群中， 在大多数患者中，佩吉特 疾病无症状。 有症状的5%患者有骨痛 以及各种各样的并发症包括骨折增加耳聋 和神经系统并发症 佩吉特最严重的并发症 疾病是骨骼的恶性转化。 虽然这些 转化是罕见的，它们对发病率有显著影响， 这种疾病的死亡率。 最常见的恶性肿瘤类型 与佩吉特病相关的转化是骨肉瘤。 此外，本发明还提供了一种方法， 佩吉特骨肉瘤患者的预后比 患有新生骨肉瘤 骨肉瘤被认为是由于 一系列的遗传改变，将成骨细胞转化为恶性肿瘤。 状态 强有力的证据表明，一个重要的肿瘤抑制基因参与了 成骨细胞的调节位于18号染色体上， （Marc汉森博士实验室）。 此外，申请人（博士） Leach）已经产生了遗传证据，证明佩吉特 在18号染色体的同一区域。 因此， 佩吉特病与骨肉瘤有很强的分子基础。 是 假设这种骨肉瘤肿瘤抑制基因和佩吉特 易感基因是相同的基因，或两个紧密连锁的基因（即，一 邻接基因综合征）。 这项研究的目的是确定这一点， 基因（或这些基因）在染色体18上，并开始，以确定他们的作用， 这两种疾病。 该提案是互动研究的一部分。 项目补助金（IRPG）开发，以实现这一目标。 汉森医生 实验室将在骨肉瘤中使用有丝分裂作图方法，而Dr。 利奇的实验室将使用减数分裂作图与许多佩吉特疾病 金斯。 鉴定这个基因（或这些基因）是重要的一步 对骨肉瘤和佩吉特病治疗的发展具有重要意义。

DESCRIPTION (Adapted from the Applicant's Abstract): Paget disease of the bone is a common bone disease characterized by abnormal osteoclasts which are large, overactive, multinucleated and contain paramyxovirus-like nuclear inclusions. It is a relatively common disorder, with an estimated incidence of 3% in individuals over the age of 40. In the majority of patients, Paget disease is asymptomatic. The 5% of patients with symptoms have bone pain and a wide range of complications including increased fractures, deafness and neurological complications. The most devastating complication of Paget disease is malignant transformation of the bone. Although these transformations are rare, they contribute significantly to the morbidity and mortality of this disorder. The most frequent type of malignant transformation associated with Paget disease is osteosarcoma. In addition, Paget patients with osteosarcoma have a much worse prognosis than patients with osteosarcoma de novo. Osteosarcomas are believed to result from a series of genetic alterations which transform the osteoblast to a malignant state. Strong evidence that an important tumor suppressor gene involved in the regulation of the osteoblast lies on chromosome 18 has recently been generated (Dr. Marc Hansen's laboratory). Furthermore, the applicant (Dr. Leach) has generated genetic evidence that there is a locus for Paget disease in the same region of chromosome 18. Thus, the correlation between Paget disease and osteosarcoma has a strong molecular basis. It is hypothesized that this osteosarcoma tumor suppressor gene and the Paget predisposition gene are the same gene, or two tightly linked genes (i.e., a contiguous gene syndrome). The goal of this research is to identify this gene (or these genes) on chromosome 18 and begin to determine their role in both of these disorders. This proposal is part of an Interactive Research Project Grant (IRPG) developed to achieve this goal. Dr. Hansen's laboratory will utilize mitotic mapping methods in osteosarcomas, while Dr. Leach's laboratory will use meiotic mapping with numerous Paget disease kindreds. Identification of this gene (or these genes) is an important step towards the development of treatment for osteosarcoma and Paget disease.