Rare Cancer Genetics Registry

描述（由申请人提供）：总体而言，罕见癌症（根据《孤儿病法案》的定义，在美国影响不到20万人的癌症）占美国癌症诊断的27%，占癌症死亡率的25%。然而，尽管新疗法改变了一些常见癌症的治疗方式，但大多数罕见癌症的治疗进展甚微，针对这些疾病的研究也很少。该提案的主要目标是扩大基础设施，并为罕见癌症遗传学登记处（RCGR）启动一个研究项目。RCGR是2009年由美国国立卫生研究院挑战基金资助的一个项目，旨在“促进对这些疾病的病因和治疗的研究”。目前，RCGR是一个拥有500多名参与者的注册中心，由马萨诸塞州总医院的一个协调中心、五个学术临床招聘网站和一个学术医学信息学网站组成。该提案计划扩大600名极罕见（在美国发病率低于5000 /年）和未充分研究的癌症参与者的登记。注册人将在5年的资助期内从5个学术临床站点和现有基金会的登记处招募。脊索瘤、葡萄膜黑色素瘤、默克尔细胞癌、外阴癌和腺样囊性癌的诊断将是招募的重点，在5年的项目期间，根据初步结果和招募的可行性选择。将获得肿瘤组织和DNA，以及关于诊断、治疗、反应和复发的图表抽象数据。注册者将同意再次联系以参与未来的研究。一项新的研究计划将启动，旨在1)描述罕见肿瘤的遗传特征，为治疗干预的选择提供信息；2)了解罕见癌症患者的反应、复发和晚期效应的临床、病理和治疗预测因素。肿瘤基因分型将使用最先进的机器人技术进行，该技术可以检测许多常见癌症中出现的一系列突变，并且潜在的靶向治疗方法已经可用或正在开发中。结果分析将需要复杂的统计方法，可以通过适当地分析登记中的患者总数来处理每个单独诊断中的少数患者。这个提议的项目可以为更广泛的研究界提供资源，并将在未来的许多年里为癌症研究服务。

DESCRIPTION (provided by applicant): Taken as an aggregate, rare cancers (those affecting fewer than 200,000 people in the US according to the Orphan Disease Act definition) account for 27% of the US cancer diagnoses and 25% of cancer mortality. However, while new therapies have changed the way some common cancers are treated, there has been little advance in the treatment of most rare cancers and research directed at these diseases is sparse. The main goal of this proposal is to expand the infrastructure and launch a research program for the Rare Cancer Genetics Registry (RCGR), a project that was funded by an NIH Challenge grant in 2009 to "promote research into the causes and treatment of these diseases". Currently, the RCGR is a registry with over 500 participants and consists of a coordinating center at Massachusetts General Hospital, five academic clinical recruiting sites, and an academic medical informatics site. This proposal plans to expand the registry by 600 participants with very rare (incidence below 5,000/year in the US) and understudied cancers. Registrants will be recruited at 5 academic clinical sites and from registries of existing foundations during the 5 years of the grant. Diagnoses of chordoma, uveal melanoma, Merkel cell carcinoma, vulvar cancer, and adenoid cystic carcinoma will be the focus of recruitment, chosen due to preliminary results and feasibility of recruitment during the 5-year project period. Tumor tissue and DNA will be obtained, along with chart-abstracted data on diagnosis, treatment, response and recurrence. Registrants will be consented for re-contact to participate in future studies. A new research program will be launched, aimed at 1) characterizing the genetic profile of rare tumors that could inform the choice of therapeutic interventions, and 2) understanding the clinical, pathological, and therapeutic predictors of outcomes of response and recurrence and late effects in rare cancer patients. The tumor genotyping will be carried out using a state-of-the-art robotic technology that detects a set of mutations that arise in many common cancers, and for which potential targeted therapies are available or in development. The outcomes analysis will require sophisticated statistical methods that can deal with the small numbers of patients within each individual diagnosis by appropriately analyzing the aggregate of patients in the registry. This proposed project could provide resources that will be available to the wider research community and will serve cancer research for many years to come. PUBLIC HEALTH RELEVANCE: Rare cancers account for a significant morbidity and mortality in the United States. This proposal aims to gain a better understanding of the factors associated with the risks and outcomes of people with these cancers in order to facilitate development of better methods of prevention and treatment.