Clinical Genetic Studies of Familial and Hereditary Cancer Syndromes

临床遗传学分会(CGB)是NCI的临床癌症遗传学翻译研究活动的基地。CGB带来了多学科的流行病学视角：了解基因在癌症的病因、治疗和预防中的作用；为高危个人和家庭制定综合管理策略；以及培训下一代临床癌症遗传学研究人员。遗传性乳腺癌/卵巢癌(HBOC)基于33个BRCA突变阳性家庭的前瞻性队列，具有广泛的临床/流行病学数据和生物样本。与这项研究相关的临床活动已经结束，但其生物样品仍在多个翻译研究项目中使用。对这些前瞻性监测家庭中乳腺癌风险的最新分析表明，来自这些突变阳性家庭的突变阴性妇女的风险与普通人群中的类似。到目前为止，已经出版了20篇临床手稿，出版了40份报告和8篇正在审查的手稿(与国际财团CIMBA合作)，阐明了BRCA相关乳腺癌和卵巢癌外显性的遗传修饰因素。遗传性骨髓衰竭综合征(IBMFS)研究针对Fanconi贫血(FA)和相关疾病，包括再生障碍性贫血、骨髓增生异常综合征(MDS)、急性髓系白血病(AML)和选定的实体瘤。我们已经招募了来自406个IBMFS家庭的1722名成员。主要发现包括对FA和先天性角化不良(DC)相关癌症风险的定量估计，确定这两种疾病的癌症风险具有惊人的相似性，扩大这些综合征的临床表型，并确定非常短的端粒是DC的病因学标志。在范可尼贫血研究基金会的资助下，我们正在撰写一份关于FA患者免疫功能的报告。我们合作开发了一种对P。

The Clinical Genetics Branch (CGB) is NCI's base for intramural clinical cancer genetics translational research activity. CGB brings a multidisciplinary, epidemiologic perspective to: Understanding the role of genes in the cause, treatment, and prevention of cancer; Developing comprehensive management strategies for high-risk individuals and families; and Training the next generation of clinical cancer genetics investigators.Hereditary Breast/Ovarian Cancer (HBOC) is based on a prospective cohort of 33 BRCA mutation-positive families with extensive clinical/epidemiologic data and biological samples. Clinical activity related to this study has ended, but its biospecimens continue to be used in multiple translational research projects. The most recent analysis of breast cancer risk in these prospectively-monitored families indicates that mutation-negative women from these mutation-positive families have risks that are similar to those seen in the general population. To date, 20 clinical manuscripts have been published and 40 reports plus 8 manuscripts under review (in collaboration with the international consortium CIMBA) elucidating genetic modifiers of BRCA-related breast and ovarian cancer penetrance have been published. Inherited Bone Marrow Failure Syndromes (IBMFS) Study targets Fanconi anemia (FA) and related disorders which include high risk of aplastic anemia, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and selected solid tumors. We have enrolled 1722 members from 406 IBMFS families. Major findings include quantitative estimates of FA- and dyskeratosis congenita (DC)-related cancer risks, identifying the striking similarity in cancer risks in these 2 disorders, expanding the clinical phenotype of these syndromes, and identifying very short telomeres as pathognomonic for DC. Under a Fanconi Anemia Research Foundation grant, we are writing a report on immune function in FA patients. We collaborated on development of an in vitro assay for p