Exploring Precision Cancer Medicine for Sarcoma and Rare Cancers

描述（由申请人提供）：癌症患者的临床管理不需要“一刀切”的方法。事实上，对人类癌症基因组景观的研究已经证明，癌症可以具有多种突变，其中一个子集可能是当前药物的“可操作”。因此，癌症治疗的个性化将需要独特和共享的遗传畸变的分子表征。特别是，患有晚期/难治性癌症并且是临床试验候选人的患者可以通过基于其特定肿瘤中的“可操作”基因来确定“靶向”药物的资格而受益。基因组测序技术的不断进步，现在已经有可能考虑在临床环境中使用序列数据。因此，高通量测序的翻译将支持癌症的“个性化”策略。然而，临床测序的翻译面临着独特的挑战，包括识别可能受益的患者，制定知情同意和人类受试者保护，概述可测量的结果，解释应该报告和验证的结果以及如何报告结果。该提案汇集了密歇根大学的专业知识，包括临床肿瘤学，癌症遗传学，基因组科学/生物信息学，临床病理学，社会和行为科学以及生物伦理学，以实施该临床癌症测序项目。我们将我们的临床测序工作集中在肉瘤和其他罕见癌症上，因为这是密歇根州的临床优势领域。三个综合项目的主题如下：项目1）“临床基因组研究”将确定符合临床试验条件的晚期或难治性肉瘤或罕见癌症患者，同意他们参加研究并获得生物标本（肿瘤组织、种系组织），存储临床数据，并组建多学科测序肿瘤委员会，以审议可操作或偶然的基因组结果的返回;项目2）“测序与分析”将处理生物标本，并对肿瘤进行全面的测序和分析，以根据CLIA/CAP指南鉴定点突变、拷贝数变化、重排/基因融合和异常基因表达;项目3）“伦理与社会心理分析”将评估临床医生和患者对知情同意过程的反应，基因组序列结果的交付，和基因组结果的使用。

DESCRIPTION (provided by applicant): The clinical management of patients with cancer does not entail a "one size fits all" approach. In fact, studies of the genomic landscape of human cancers have demonstrated that cancers can have a multitude of mutations, a subset of which may be "actionable" with current drugs. Thus, the personalization of therapy for cancer will require molecular characterization of unique and shared genetic aberrations. In particular, patients who have advanced / refractory cancer and are candidates for clinical trials could potentially benefit by identifying eligibility for "targeted" drugs based on the "actionable" genesin their specific tumor. Growing technological advances in genomic sequencing has now made it possible to consider the use of sequence data in a clinical setting. Thus, the translation of high throughput sequencing would support a "personalized" strategy for cancer. However, the translation of clinical sequencing bears unique challenges including identifying patients who could benefit, developing informed consent and human subjects protections, outlining measurable outcomes, interpreting what results should be reported and validated, and how results should be reported. This proposal brings together expertise at the University of Michigan including clinical oncology, cancer genetics, genomic science/bioinformatics, clinical pathology, social and behavioral sciences, and bioethics in order to implement this clinical cancer sequencing project. We have focused our clinical sequencing effort on sarcomas and other rare cancers as this is an area of clinical strength at Michigan. Three integrated Projects have the following themes: Project 1) "Clinical Genomic Study" will identify patients with advanced or refractory sarcoma or rare cancers who are eligible for clinical trials, consent them to the study obtain biospecimens (tumor tissue, germline tissue), store clinical data, and assemble a multi-disciplinary Sequencing Tumor Board to deliberate on return of actionable or incidental genomic results; Project 2) "Sequencing & Analysis" will process biospecimens and perform comprehensive sequencing and analysis of tumors to identify point mutations, copy number changes, rearrangements/gene fusions, and aberrant gene expression under CLIA/CAP guidelines; Project 3) "Ethics & Psychosocial Analysis" will evaluate the clinician and patient response to the informed consent process, delivery of genomic sequence results, and use of genomic results.