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.

临床分子分析核心（CMPC）是一种协作核心，试图超越其他实验室核心的共同服务范式。其人员的专业知识允许从项目开始，例如协议开发，通过进行测定和生物统计分析。目前，我们的主要功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的姊妹中心进行了合作。这些合作的状态范围从初步讨论到协议开发，应计和分析以及完成，到出版；对于那些完成的人，我们期待参与后续研究。许多研究是临床试验测试或鉴定早期临床试验的药物。这些研究包括：“转移性尿路上皮和泌尿生殖器癌中Cabonivo或Cabonivoip的1阶段研究”以及与NCI/CCR GIST诊所的相互作用。过去，我们支持“用于晚期胸腔恶性肿瘤的分子分析和有针对性的治疗：一种生物标志物衍生的，多级别的，多层，多组织学期篮子试验”，以及在功能上定义的治疗靶标的试验，用于弥漫性固有性pontine gliomamoma中的治疗靶标”，最近使用Shukla et nibles for Neveral cellip for Leaval carter cylip vellip vellip，使用LENUGS callip sendips vernip carter。但是，其他研究更专注于理解特定疾病的潜在病理，而不是直接测试治疗。这些研究包括Oltmann等人的出版物，非整倍性，TP53突变以及MYC的扩增与肿瘤内异质性的增加以及乳腺癌患者和Hirsh的预后不良相关。值得注意的是，资源已致力于在我们的CLIA [临床实验室改进修正案]实验室中使用Illumina下一代测序实现临床外显子组和多基因面板高深度测序。为了支持这些研究，CMPC在许多分子技术方面具有专业知识，用于分析人类标本的DNA和RNA。在CMPC中使用的其他艺术测定法是包括：RNA-SEQ，mRNA表达分析（微阵列，实时PCR，基于珠子的），表观基因组甲基化（微阵列），阵列比较基因组杂交（微阶层）和端粒长度的范围。重要的是，CMPC为所有这些测定法提供了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