Clinical Genetic Studies of Familial and Hereditary Cancer Syndromes

临床遗传学分部（CGB）是NCI内部临床癌症遗传学转化研究活动的基地。CGB从多学科、流行病学的角度来理解基因在癌症的起因、治疗和预防中的作用；为高危个人和家庭制定综合管理战略；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）是基于33个BRCA突变阳性家庭的前瞻性队列研究，具有广泛的临床/流行病学数据和生物样本。与本研究相关的临床活动已经结束，但其生物标本继续用于多个转化研究项目。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一般人群相似。迄今为止，已经发表了20篇临床论文，40篇报告和8篇正在审查的论文（与国际联盟CIMBA合作），阐明了brca相关乳腺癌和卵巢癌外显率的遗传修饰因子。遗传性骨髓衰竭综合征（IBMFS）研究针对范可尼贫血（FA）及相关疾病，包括再生障碍性贫血、骨髓增生异常综合征（MDS）、急性髓性白血病（AML）和特定实体瘤。我们招收了来自406个IBMFS家庭的1722名成员。主要发现包括定量估计FA-和先天性角化不良（DC）相关的癌症风险，确定这两种疾病的癌症风险惊人的相似性，扩大这些综合征的临床表型，并确定非常短的端粒是DC的病理特征。在范可尼贫血研究基金会的资助下，我们正在撰写一篇关于FA患者免疫功能的报告。我们合作开发了一种体外检测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