Developing a genomic approach for cancer screening

描述(由申请人提供)：通过筛查及早发现癌症已被证明有助于提高几种常见恶性肿瘤的存活率。然而，筛查伴随着巨大的风险和费用。所有筛查测试面临的一个重要问题是，在尽可能多地检测癌症的同时，将假阳性的识别降至最低。假阳性筛查结果会引起患者及其家人的焦虑，需要额外昂贵的测试，如果后续研究导致并发症，可能会造成伤害。我们建议开发一种新的基因组方法用于癌症筛查，该方法利用从癌症基因组的高通量重新测序中获得的见解。我们将在肺癌的背景下开发这种方法，因为它是癌症死亡的头号原因，而且最近显示低剂量计算机体层摄影(CT)筛查在高危患者中产生了显著的生存益处。然而，低剂量CT肺癌筛查的阳性筛查结果中约95%是假阳性，因此显然需要改进。该提案描述了我们开发、优化和测试我们的方法的计划。我们将进行临床前和临床评估，并将在多个环境中测试我们的方法，包括作为区分真阳性和假阳性筛查结果的二次筛查程序和作为主要筛查方式。重要的是，该方法很容易扩展到任何可以获得高通量测序数据的癌症，我们预计最终能够使用单一分析来筛查最常见的癌症。

DESCRIPTION (provided by applicant): Early detection of cancer via screening has been shown to lead to improved survival for several common malignancies. However, screening comes with significant risks and expenses. One important issue faced by all screening tests is detecting as many cancers as possible while minimizing identification of false positives. False positive screening results induce anxiety in patients and their families, require additional expensive tests, and may result in harm if a follow-up study leads to a complication. We propose to develop a novel, genomic approach for cancer screening that leverages insights gained from high throughput re-sequencing of cancer genomes. We will develop this method in the context of lung cancer, since it is the number one cause of cancer deaths and since low dose computed tomography (CT) screening has recently been shown to produce significant survival benefits in high-risk patients. However, ~95% of positive screening results from low dose CT lung cancer screenings are false positives and so improvements are clearly needed. This proposal describes our plan to develop, optimize, and test our method. We will perform both pre-clinical and clinical evaluations and will test our approach in multiple settings, includig as a secondary screening procedure for differentiating between true positive and false positive screening results and as a primary screening modality. Importantly, the method is readily extendable to any cancer for which high throughout sequencing data are available and we envision ultimately being able to screen for most common cancers using a single assay.