Integrative Oncogenomics of Multiple Myeloma

我们的骨髓瘤研究小组已经开发了许多新靶点和新疗法（DFCI），将与世界领先的MM （IFM）合作进行合作临床和移植试验，以进行合作转化研究。我们将结合新疗法与大剂量治疗和移植，然后描述临床和生物学结果的基因组和分子相关性。项目1将通过招募1000名IFM和DFCI之间的新诊断患者，一方面侧重于确定对新型联合治疗反应的持久性，另一方面侧重于确定高剂量治疗的附加价值。该试验将提供来自新诊断和统一治疗的患者的1000个样本，以全面表征MM基因组和表观基因组，定义驱动MM发展和进展的分子事件（项目2），以及确定新的治疗靶点（项目3），生物标志物和预防策略（项目4）。在这些合作研究中，拥有全基因组测序能力的英国桑格研究所（Sanger Institute）将与DFCI和IFM的研究团队一起，对患者样本进行分子遗传学分析，并描绘最有可能做出反应并延长生存期的患者亚组（项目2和4）。利用这些高通量基因组技术确定的临床相关新靶点将在项目3中得到验证，并开发新的靶向治疗方法。Project 4将进一步分析复发时基因组变化的演变及其临床意义，并制定预防基因组不稳定的策略。这4个项目将由行政和沟通核心(A)、临床和组织核心(B)支持；Genomics Core (C)；基因组测序核心(0)和生物统计学和生物信息学核心(E)。这种独特的合作努力将为这种目前无法治愈的疾病定义一个新的治疗范例。

Our myeloma research group, which has developed number of new targets and novel therapies (DFCI), will partner with the world leaders in cooperative clinical and transplantation trials in MM (IFM) to pursue collaborative translational investigation. We will couple combination novel therapies with high dose therapy and transplantation and then delineate genomic and molecular correlates of clinical and biological outcomes. Project 1 will focus on defining the durability of responses to novel combination therapy on the one hand, and the additional value of high dose therapy on the other, by enrolling 1000 newly diagnosed patients between IFM and DFCI. This trial will provide 1000 samples from newly diagnosed and uniformly treated patients to comprehensively characterize the MM genome and epigenome, to define molecular events driving development and progression of MM (Project 2), as well as to identify novel therapeutic targets (Project 3), biomarkers, and preventative strategies (Project 4). In these collaborative studies the Sanger Institute in UK, with whole genome sequencing capabilities, along with research teams from DFCI and IFM, will perform molecular genetic analysis of patient samples and delineate patient subgroups most likely to respond and achieve prolonged survival (Projects 2 and 4). The clinically relevant novel targets identified using these high throughput genomic technologies will be validated and novel targeted therapies developed in Project 3. Project 4 will further analyze evolution of genomic changes at relapse and their clinical significance, as well as devise strategies to prevent genomic instability. These 4 projects will be supported by Administrative and Communication Core (A), Clinical and Tissue Core (B); Genomics Core (C); Genomic Sequencing Core (0), and Biostatistical and Bioinformatics Core (E). This unique collaborative effort will define a new treatment paradigm for this presently incurable disease.