Lung Cancer Mutation Analysis

描述（由申请人提供）：摘要本项目旨在建立一个肺癌突变联盟（LCMC），由13个对肺癌和肺癌基因组检测感兴趣的机构组成，这些机构在肺癌方面拥有主要的NCI赠款。LCMC成员将在拟议的临床试验中收集1000例晚期肺腺癌患者的相关临床、病理和基因组数据。基因组检测将根据联合体方案在位于联合体机构的CLIA认证实验室进行。该方案将确定每种遗传变化的频率;遗传变化、临床特征和结局之间的关联;以及不同遗传变化之间的关联。这些信息将用于验证和/或改变腺癌的病理学亚分类。遗传分析将用于确定具有特定遗传变化的患者是否有资格入组评价针对特定突变/扩增/融合基因的新型靶向治疗的治疗性试验。这些治疗试验由其他机制资助。该提案将导致设立至少16个新职位，并购买用于基因检测的设备和试剂。试验结果和LCMC的建立将加速肺癌个性化医疗的实施。 公共卫生相关性：相关性肺癌是美国男性和女性癌症死亡的主要原因，占所有癌症死亡人数的30%。大约一半的肺癌患者存在晚期疾病，标准化疗组合仅产生适度的生存改善，伴随着相关的高毒性率、静脉给药的不便和高成本。最近的分子研究表明，多达50%的肺癌在已知的癌基因中具有激活突变，已经开发了新的治疗药物。早期的临床试验表明，靶向口服药物比化疗毒性更小，获益更大，但仅适用于具有特定突变癌基因的患者。这项应用中的新技术将允许大量肺癌患者对这些新描述的癌基因进行分子检测，以便我们能够了解它们作为新靶向药物受益的预测因子的频率，相关性和重要性。这一建议将加速肺癌和其他癌症的个性化医疗的发展。

DESCRIPTION (provided by applicant): Abstract this project aims to establish a Lung Cancer Mutation Consortium (LCMC) consisting of 13 institutions with a major interest in lung cancer and genomic testing of lung cancer as documented by having major NCI grants in lung cancer. The LCMC members will collect linked clinical, pathologic and genomic data on 1000 patients with advanced adenocarcinoma of the lung in the proposed clinical trial. The genomic tests will be conducted in CLIA certified laboratories located at consortium institutions according to consortium protocols. The protocol will determine the frequency of each genetic change; the association between the genetic change, the clinical features, and the outcome; and the association between different genetic changes. The information will be used to validate and/or change the pathologic sub-classification of adenocarcinomas. The genetic analyses will be used to determine if patients with specific genetic changes are eligible for enrollment into therapeutic trials evaluating novel targeted therapies directed at the specific mutation / amplification / fusion gene. These therapeutic trials are funded by other mechanisms. The proposal will lead to the creation of at least 16 new positions and to the purchase of equipment and reagents for the genetic testing. The trial results and the establishment of the LCMC will hasten the implementation of personalized medicine for lung cancer. PUBLIC HEALTH RELEVANCE: Relevance Lung cancer is the leading cause of cancer death in men and women in the U.S., accounting for about 30% of all cancer deaths. About half of all lung cancer patients present with advanced disease for which standard chemotherapy combinations produce only modest survival improvement with the associated high toxicity rates, inconvenience of intravenous administration and high costs. Recent molecular studies showed that as many as 50% of lung cancer have activating mutations in known oncogenes to which novel therapeutic agents have been developed. Early clinical trials suggest that targeted oral agents have less toxicity and greater benefit than chemotherapy but only when administered to patients with the specific mutated oncogene. The new technologies in this application will allow a large number of lung cancer patients to have molecular tests for these newly described oncogenes so that we can understand their frequency, relevance and importance as predictors to benefit from the new targeted agents. This proposal will hasten the development of personalized medicine for lung cancer and other cancers as well.