Molecular Profiling of Clinical Specimens

临床分子分析核心（CMPC）是一个协作核心，旨在超越其他核心的通用服务范式。人员的专业知识使我们能够从项目开始就参与其中，例如方案制定，以及检测和生物统计分析的性能。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）和临床中心的许多分支机构合作。许多临床合作涉及CCR的许多分支，如医学肿瘤学，皮肤病学，泌尿肿瘤学，病理学实验室，儿科肿瘤学，代谢学和放射肿瘤学。这些合作的状态包括从初步讨论到方案制定、累积和分析以及完成。对于那些已经完成的，我们期待参与后续研究。许多研究都是临床试验，在I期或II期测试药物或新的联合疗法。这些研究包括索拉非尼和贝伐单抗治疗难治性、转移性或不可切除的实体瘤患者；泛her抑制剂PF-00299804在非小细胞肺癌中的作用R1507 II期研究的全组生物学和银行研究Belinostat在既往含铂化疗复发或转移性不可切除胸腺瘤或胸腺癌患者中的II期研究Vandetanib （ZD6474 Zactima）治疗遗传性甲状腺髓样癌儿童和青少年的I/II期临床试验小儿脑桥神经胶质瘤基因组畸变的鉴定AKT抑制剂磷酸三西瑞滨和厄洛替尼（特罗凯）在表皮生长因子受体（EGFR）抑制剂耐药或初治的晚期肺癌或其他实体肿瘤患者中的I期研究ERBB4突变携带者IV期黑色素瘤患者拉帕替尼治疗的II期试验；ZD6474 （Vandetanib AZCTIMA）联合蛋白酶体抑制剂硼替佐米（Velcade）治疗成人实体瘤，重点是遗传性或散发性、局部晚期或转移性甲状腺髓样癌（MTC）的靶向I期临床试验；临床GIST基因突变的临床鉴定基因型靶向抗mapk通路治疗胰腺癌的研究种系肾癌基因的基因组检测以及晚期非小细胞肺癌、小细胞肺癌和胸腺恶性肿瘤的分子分析和靶向治疗的试点试验。然而，其他研究更侧重于了解特定疾病的潜在病理，而不是直接测试一种治疗方法。这些研究包括：暴露于紫外线辐射的成人和儿童的基因表达谱和光毒性；慢性移植物抗宿主病干细胞移植患者的临床评价和实验室研究遗传性泌尿系统恶性疾病的临床表现及分子基础活检证实或怀疑恶性肿瘤患者血清和组织标本的采集滤泡性淋巴瘤的大规模甲基化分析小细胞肺癌的分子特征分析胸腺瘤亚群的分子谱分析白血病生物学研究；中国食管癌；前列腺癌激光捕获显微解剖及微环境评价毛细胞白血病患者免疫毒素耐药性的研究胶质瘤干细胞甲基化变化及其亚型的研究甲状腺髓样癌的自然历史，特别是在MEN 2患者中，以及参与肿瘤发生和对靶向治疗产生耐药性的分子途径；非裔美国人和欧裔美国人乳腺癌患者DNA甲基化分析探讨家族性慢性淋巴细胞白血病风险与单克隆b细胞淋巴细胞增多症的关系胃肠道肿瘤放射治疗患者的生物标志物和放射副作用。去年又增加了8个合作项目，包括：Ponatinib治疗晚期或转移性甲状腺髓样癌的II期研究；COXEN算法用于晚期尿路上皮癌个体化治疗敏感性预测的可行性研究γ -分泌酶抑制剂PF-03084014治疗侵袭性硬纤维瘤成人的II期临床试验；端粒长度和甲基化在肝细胞癌中的作用。值得注意的是，资源已经开始投入到使用Illumina下一代测序仪实现临床外显子组测序。为了支持这些研究，CMPC在许多分子技术方面拥有专业知识，用于分析人类标本的DNA和RNA。在广泛的先进平台上发现的最先进的分析包括：DNA测序（Sanger和下一代测序），mRNA表达分析（微阵列，实时PCR，基于珠状细胞的），表观基因组甲基化（微阵列和焦磷酸测序），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了完整的生物信息学支持。

The Clinical Molecular Profiling Core (CMPC) is a collaborative core that seeks to go beyond the common service paradigm of other cores. The expertise of the personnel allows us to be involved from the start of a project, such as the protocol development, though performance of the assay and biostatistical analysis. 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) and the Clinical Center. Many dozen clinical collaborations have involved many of the branches in CCR such as Medical Oncology, Dermatology, Urologic Oncology, Laboratory of Pathology, Pediatric Oncology, Metabolism, and Radiation Oncology. The status of these collaborations range from preliminary discussions through protocol development, accrual and analysis, and completion. For those that are completed, we look forward to being involved in follow up studies. Many of the studies are clinical trials testing drugs in phase I or II or new combination therapies. These include studies such as Sorafenib and Bevacizumab in Treating Patients With Refractory, Metastatic or Unresectable Solid Tumors; Pan-HER Inhibitor PF-00299804 in Non-Small Cell Lung Cancer; a Group Wide Biology and Banking Study for Phase II Studies of R1507; Phase II Study of Belinostat in Patients With Recurrent or Metastatic Unresectable Thymoma or Thymic Carcinoma Previously Treated With Prior Platinum-Containing Chemotherapy; Phase I/II trial of Vandetanib (ZD6474 Zactima) in Children and Adolescents with Hereditary Medullary Thyroid Carcinoma; Identifying Genomic Aberrations in Pediatric Pontine Glioma; Phase I Study of the AKT inhibitor Triciribine Phosphate Monohydrate and Erlotinib (Tarceva) in Subjects with Advanced Lung Cancer or other Solid Tumors Who are Resistant to or Naive to Epidermal Growth Factor Receptor (EGFR) Inhibitors; Phase II trial in patients with stage IV melanoma for lapatinib treatment when they are ERBB4 mutation carriers; Targeted Phase I Trial of ZD6474 (Vandetanib AZCTIMA) plus the Proteasome Inhibitor Bortezomib (Velcade) in Adults with Solid Tumors with a Focus on Hereditary or Sporadic, Locally Advanced or Metastatic Medullary Thyroid Cancer (MTC); Clinical identification of gene mutations clinical GIST; Genotype-directed anti-MAPK pathway therapy in pancreas cancer; Genomic testing of germline renal cancer genes; and a Pilot Trial of Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies. However, other investigations are more focused on understanding the underlying pathology of specific diseases and are not directly testing a therapy. These studies include: Gene Expression Profiling and Phototoxicity in Adults and Children Exposed to Ultraviolet Radiation; Clinical Evaluations and Laboratory Studies in Patients With Chronic Graft-Versus-Host Disease Who Have Undergone a Stem Cell Transplant; Clinical Manifestations and Molecular Bases of Heritable Urologic Malignant Disorders; Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease; Large Scale Methylation Analysis of Follicular Lymphoma; Molecular Profiling of Small Cell Lung Cancer; Molecular Profiling of Thymoma Subsets; Leukemia Biology Study; Esophageal Carcinoma in China; Laser Capture Microdissection and Evaluation of the Microenvironment in Prostate Cancer; Immunotoxin Resistance in Patients with Hairy Cell Leukemia; Understanding the methylation changes and subtypes in glioma stem cells derived from glioblastoma; The natural history of Medullary Thyroid Carcinoma, particularly in patients with MEN 2, and the molecular pathways involved in tumorigenesis and the development of resistance to targeted therapies; Analysis of global DNA methylation in breast tumors of African-American and European-American patients; Examine the association between risk of familial chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis; and Biomarkers and Radiation Side Effects in Patients Undergoing Radiation Therapy for Gastrointestinal Cancer. In the last year eight additional collaborations have been added and they include: A Phase II Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer; A Feasibility Study using COXEN Algorithm for Individualized Therapeutic-Sensitivity Prediction in Patients with Advanced Urothelial Cancer; Phase II trial of the gamma-secretase inhibitor PF-03084014 in adults with desmoid tumors/aggressive; and Telomere length and methylation in hepatocellular carcinoma. Significantly, resources have begun to be devoted to actualizing clinical exome sequencing using Illumina next-generation sequencers. To support these studies, the CMPC has expertise in many molecular technologies for the analysis of DNA and RNA from human specimens. State of the art assays found on a wide range of advanced platforms include: DNA sequencing (Sanger and next-generation sequencing), mRNA expression analysis (microarray, real-time PCR, bead-based), epigenomic methylation (microarray and pyrosequencing), array comparative genomic hybridization (microarray), and telomere length assays. Importantly, the CMPC provides full bioinformatics support for all these assays.