Molecular Profiling of Clinical Specimens

临床分子图谱核心(CMPC)是一个寻求超越其他核心的公共服务范例的协作核心。人员的专业知识使我们能够从项目的开始就参与进来，例如方案的制定，通过分析和生物统计分析的表现。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进行了合作。50多项临床协作涉及CCR的许多分支，如内科肿瘤学、皮肤科、泌尿外科肿瘤学、病理实验室、儿科肿瘤学、代谢和放射肿瘤学。这些协作的状况从初步讨论到制定议定书、积累和分析以及完成。对于那些已经完成的研究，我们期待着参与后续研究。许多研究都是临床试验，测试I期或II期药物或新的联合疗法。这些研究包括：索拉非尼和贝伐单抗用于治疗难治性、转移性或无法切除的实体肿瘤患者，泛HER抑制剂PF-00299804用于非小细胞肺癌，R1507第二阶段研究的全组生物学和银行研究，贝立诺斯特用于复发或转移、不能切除的胸腺瘤或胸腺癌患者的第二阶段研究，先前接受含铂化疗的患者，Vandetanib(ZD6474，Zactima)在儿童和青少年遗传性髓样甲状腺癌中的I/II期试验，确定儿童桥脑胶质瘤、儿童桥脑胶质瘤和胸腺癌的基因组异常在对表皮生长因子受体(EGFR)抑制剂耐药或幼稚的晚期肺癌或其他实体肿瘤患者中，AKT抑制剂一水合磷酸三西核苷和厄洛替尼(Tarceva)的I期研究，当患者是ERBB4突变携带者时，对IV期黑色素瘤患者进行拉帕替尼治疗的II期试验，ZD6474(Vandetanib；AZCTIMA)加蛋白酶体抑制剂Bortezomib(VELCADE)用于治疗遗传性或散发性、局部晚期或转移性甲状腺髓样癌(MTC)的成人实体肿瘤，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图谱和靶向治疗试点试验。然而，其他研究更侧重于了解特定疾病的潜在病理，而不是直接测试治疗方法。这些研究包括：紫外线照射下成人和儿童的基因表达谱和光毒性，干细胞移植后慢性移植物抗宿主病患者的临床评估和实验室研究，遗传性泌尿系恶性肿瘤的临床表现和分子基础，经活检证实或疑似恶性疾病患者的血清和组织样本收集，滤泡性淋巴瘤的大规模甲基化分析，小细胞肺癌的分子谱分析，胸腺瘤亚群的分子谱分析，白血病生物学研究，中国的食道癌，激光捕获显微解剖和前列腺癌微环境的评估，毛细胞白血病患者的免疫毒素耐药性，胃肠道肿瘤放射治疗患者的生物标志物和辐射副作用。为了支持这些研究，CMPC拥有从人类样本中分析DNA、RNA和蛋白质的许多分子技术方面的专业知识。在各种先进平台上发现的最先进的分析方法包括：DNA测序(Sanger和下一代测序)、信使核糖核酸表达分析(微阵列、实时聚合酶链式反应、珠基)、表观基因组甲基化(微阵列和焦测序)、阵列比较基因组杂交(微阵列)和组织微阵列。重要的是，CMPC为所有这些检测提供全面的生物信息学支持。

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. Over five 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, a 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, a phase II trial in patients with stage IV melanoma for lapatinib treatment when they are ERBB4 mutation carriers, a 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), 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, and Biomarkers and Radiation Side Effects in Patients Undergoing Radiation Therapy for Gastrointestinal Cancer. To support these studies, the CMPC has expertise in many molecular technologies for the analysis of DNA, RNA and protein 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 tissue microarrays. Importantly, the CMPC provides full bioinformatics support for all these assays.