THE MOLECULAR BASIS OF FAMILIAL CANCER PREDISPOSITION SYNDROMES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要 已知某些遗传综合征使受影响的患者比一般人群更易患癌症。 对于其中一些疾病，遗传缺陷已在人类中得到表征;在其他疾病中，酵母或动物模型的研究正在提供有关疾病遗传基础的早期答案。 仍然有许多罕见的遗传性疾病远未在遗传水平上得到表征。 对于这些疾病，需要在临床层面收集原始数据。 由于它们是世界范围内罕见的疾病，积累受影响的患者及其亲属以研究他们的遗传物质成为一项艰巨的任务。 这项研究将允许从患者及其家庭成员中收集样本，以便进行分子和遗传研究，以更好地了解原发综合征和癌症发展的易感性。 假设 在临床和分子水平上研究罕见的癌症易感综合征将有助于深入了解普通人群中癌症的发病机制。 具体目标 1. 从家族性癌症综合征患者及其家庭成员中收集并分析临床样本。 家族性癌症综合征包括例如家族性结肠癌、家族性乳腺-卵巢癌、共济失调性血管扩张症、布卢姆综合征、着色性干皮病和Rothmund-Thomson综合征（RTS）的实例。 样本将包括血液，组织（正常和肿瘤）和体液，这些样本将提供给研究人员进行研究，以帮助定义和描述导致这些遗传性疾病及其癌症倾向的潜在遗传缺陷。 2. 收集和分析受家族性癌症综合征影响的患者及其家庭成员的医疗记录。 临床信息将允许结合分子研究进行基因型-表型分析。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT Certain genetic syndromes are known to predispose affected patients to cancer more than the general population. For some of these disorders, the genetic defect has been characterized in humans; in others, studies in yeast or animal models are providing early answers regarding the genetic basis for disease. There are still many rare inherited disorders that are far from being characterized at the genetic level. For these disorders, primary data needs to be gathered at the clinical level. Because they are rare disorders worldwide, accumulating affected patients and their relatives in order to study their genetic material becomes a difficult task. This study would allow the collection of samples from patients and their family members so that molecular and genetic studies can be conducted to better understand both the primary syndrome and the predisposition toward cancer development. HYPOTHESIS Studying rare cancer predisposition syndromes both at the clinical and molecular level will provide insight into the pathogenesis of cancer in the general population. SPECIFIC AIMS 1. Collect and alaynze clinical samples from both patients affected by a familial cancer syndrome and their family members. Familial cancer syndromes include examples such as familial colon cancer, familial breast-ovarian cancer, ataxiatelangiectasia, Bloom's syndrome, xeroderma pigmentosa, and Rothmund-Thomson Syndrome (RTS). Samples would include bood, tissues (normal and tumor) and body fluids which would be made available to investigators for the purpose of conducting research that will help to define and characterize the underlying genetic defects which cause these inherited disorders and their propensity toward cancer. 2. Collect and analyze medical records from both patients affected by a familial cancer syndrome and their family members. Clinical information will allow genotype-phenotype analyses in combination with molecular studies.