Molecular Profiling of Clinical Specimens

临床样本的分子分析

• 批准号: 10262744
• 负责人: Daniel Edelman
• 金额: $ 130.75万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10262744
• 关键词: Aneuploidy; Bioinformatics; Biological Assay; Biological Markers; Biometry; Breast Cancer Patient; CCR; Clinic; Clinical; Clinical Investigator; Clinical Laboratory Improvement Amendments; Clinical Trials; Collaborations; Crohn' s disease; DNA analysis; Data; Diffuse intrinsic pontine glioma; Disease; Follow-Up Studies; Genetic Transcription; Genome; Genomics; Human; Human Resources; Investigation; Laboratories; Length; Malignant neoplasm of lung; Malignant neoplasm of thorax; Medicine; Methylation; MicroRNAs; Molecular; Molecular Analysis; Molecular Profiling; Mutation; NCI Center for Cancer Research; National Cancer Institute; Pathology; Performance; Pharmaceutical Preparations; Phase; Property; Publications; RNA; Resources; Scientific Advances and Accomplishments; Services; Sister; Specimen; TP53 gene; Technology; Testing; Therapeutic; Time; Tumor Biology; Urogenital Cancer; Urothelium; Ursidae Family; Vision; base; cancer genome; cancer therapy; colon carcinogenesis; comparative genomic hybridization; early phase clinical trial; epigenomics; exome; gene panel; genome analysis; induced pluripotent stem cell; mRNA Expression; molecular targeted therapies; next generation sequencing; novel; outcome forecast; personalized cancer care; phase 1 study; precision medicine; programs; protocol development; stem cell model; targeted treatment; telomere; therapeutic target; tool; transcriptome sequencing; tumor; tumor heterogeneity

The Clinical Molecular Profiling Core (CMPC) is a collaborative core that seeks to go beyond the common service paradigm of other laboratory cores. The expertise of its personnel allows involvement from the start of a project, such as the protocol development, through performance of the assay and biostatistical analyses. Currently, our main function is to support clinical trials at the National Cancer Institute (NCI) and to that end we have collaborations with many of the branches in the Center for Cancer Research (CCR/NCI) and sister centers in the NCI. The status of these collaborations range from preliminary discussions through protocol development, accrual and analysis, and completion to publication; for those that are completed, we look forward to being involved in follow up studies. Many of the studies are clinical trials testing or identifying drugs for early phase clinical trials. These include studies such as: "Phase 1 study of CaboNivo or CaboNivoIp in Metastatic Urothelial and Genitourinary Cancer" and interactions with the NCI/CCR GIST Clinic. In the past we have supported "Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial" and a trial in "Functionally defined therapeutic targets in diffuse intrinsic pontine glioma" and recently Shukla et al., Identification of Novel Targets for Lung Cancer Therapy Using an Induced Pluripotent Stem Cell Model, 2018. However, other investigations are more focused on understanding the underlying pathology of specific diseases and are not directly testing a therapy. These studies included publications by Oltmann et al., Aneuploidy, TP53 mutation, and amplification of MYC correlate with increased intratumor heterogeneity and poor prognosis of breast cancer patients and Hirsh, et al., Dynamics of genome alterations in Crohn's disease associated colorectal carcinogenesis. Significantly, resources have been devoted to actualizing clinical exome and multi-gene panel hi-depth sequencing using Illumina next-generation sequencing in the context of our CLIA [Clinical Laboratory Improvement Amendments] laboratory. To support these studies, the CMPC has expertise in many molecular technologies for the analysis of DNA and RNA from human specimens. Other state of the art assays utilized in the CMPC are a wide range of advanced platforms that include: RNA-seq, mRNA expression analysis (microarray, real-time PCR, bead-based), epigenomic methylation (microarray), array comparative genomic hybridization (microarray), and telomere length assays. Importantly, the CMPC provides full bioinformatics support for all these assays.

临床分子图谱核心(CMPC)是一个寻求超越其他实验室核心的公共服务范例的协作核心。其人员的专业知识使其能够从项目开始就参与，如方案制定，直到化验和生物统计分析的执行。目前，我们的主要职能是支持国家癌症研究所(NCI)的临床试验，为此，我们与癌症研究中心(CCR/NCI)的许多分支机构和NCI的姐妹中心进行了合作。这些协作的情况从初步讨论到制定议定书、积累和分析、完成到出版；对于已完成的协作，我们期待着参与后续研究。许多研究都是临床试验，测试或确定早期临床试验的药物。这些研究包括：“CaboNivo或CaboNivoIp在转移性尿路上皮癌和泌尿生殖系癌中的第一阶段研究”以及与NCI/CCR GIST诊所的互动。在过去，我们曾支持“晚期胸部恶性肿瘤的分子图谱和靶向治疗：生物标记物衍生的多臂多组织学II期篮子试验”和“弥漫性固有桥脑胶质瘤的功能定义治疗靶点”试验，最近Shukla等人，2018年，使用诱导多能干细胞模型识别肺癌治疗的新靶点。然而，其他研究更侧重于了解特定疾病的潜在病理，而不是直接测试治疗方法。这些研究包括Oltmann等人发表的文章，非整倍体、TP53突变和MYC扩增与乳腺癌患者肿瘤内异质性增加和预后不良相关，以及Hirsh等人发表的与克罗恩病相关的结直肠癌发生中的基因组改变的动力学。值得注意的是，我们已经投入资源在我们的CLIA[临床实验室改进修正案]实验室中使用Illumina下一代测序实施临床外显子组和多基因小组高深度测序。为了支持这些研究，CMPC拥有从人类样本中分析DNA和RNA的许多分子技术方面的专业知识。CMPC中使用的其他最先进的分析方法是广泛的先进平台，包括：RNA-seq、mRNA表达分析(微阵列、实时聚合酶链式反应、珠基)、表观基因组甲基化(微阵列)、阵列比较基因组杂交(微阵列)和端粒长度分析。重要的是，CMPC为所有这些检测提供全面的生物信息学支持。

项目成果

Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.

• DOI: 10.1038/nm.3855
• 发表时间: 2015-06
• 期刊: Nature medicine
• 影响因子: 82.9
• 作者: Grasso CS;Tang Y;Truffaux N;Berlow NE;Liu L;Debily MA;Quist MJ;Davis LE;Huang EC;Woo PJ;Ponnuswami A;Chen S;Johung TB;Sun W;Kogiso M;Du Y;Qi L;Huang Y;Hütt-Cabezas M;Warren KE;Le Dret L;Meltzer PS;Mao H;Quezado M;van Vuurden DG;Abraham J;Fouladi M;Svalina MN;Wang N;Hawkins C;Nazarian J;Alonso MM;Raabe EH;Hulleman E;Spellman PT;Li XN;Keller C;Pal R;Grill J;Monje M
• 通讯作者: Monje M