THE MOLECULAR BASIS OF FAMILIAL CANCER PREDISPOSITION SYNDROMES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要 众所周知，某些遗传综合征比普通人群更容易使受影响的患者患上癌症。对于其中一些疾病，遗传缺陷是人类的特征；在另一些疾病中，对酵母或动物模型的研究正在提供关于疾病遗传基础的早期答案。仍有许多罕见的遗传性疾病远未在基因水平上表现出来。对于这些疾病，需要在临床层面收集主要数据。由于它们在世界各地都是罕见的疾病，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人那里收集样本，以便进行分子和遗传学研究，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.收集和分析家族性癌症综合征患者及其家属的临床样本。家族性癌症综合征包括家族性结肠癌、家族性乳腺癌-卵巢癌、共济失调血管扩张症、Bloom综合征、色素性干皮病和Rothmund-Thomson综合征(RTS)。样本将包括乳房发育不良、组织(正常和肿瘤)和体液，研究人员将获得这些样本，以进行研究，帮助定义和表征导致这些遗传性疾病的潜在遗传缺陷及其癌症倾向。 2.收集和分析家族性癌症综合征患者及其家人的医疗记录。临床信息将使基因-表型分析与分子研究相结合。

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.