Molecular Profiling of Clinical Specimens

临床样本的分子分析

• 批准号: 8763749
• 负责人: Daniel Edelman
• 金额: $ 171.67万
• 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/8763749
• 关键词: Adolescent; Adult; Adverse effects; African American; American; B-Lymphocytes; BAY 54-9085; Bioinformatics; Biological Assay; Biological Markers; Biology; Biopsy; Bortezomib; Child; Childhood; China; Chronic Lymphocytic Leukemia; Clinical; Clinical Investigator; Clinical Trials; Collaborations; Collection; Combined Modality Therapy; DNA Methylation; DNA Sequence; DNA analysis; Data; Dermatology; Disease; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Esophageal carcinoma; European; Evaluation; Follicular Lymphoma; Follow-Up Studies; Gene Expression Profiling; Gene Mutation; Genome; Genomics; Genotype; Glioblastoma; Glioma; Hairy Cell Leukemia; Human; Human Resources; Immunotoxins; Inherited; Investigation; Laboratories; Laboratory Study; Lymphocytosis; MAP Kinase Gene; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Mammary Neoplasms; Medical Oncology; Medicine; Messenger RNA; Metabolism; Methylation; MicroRNAs; Microarray Analysis; Molecular; Molecular Profiling; Molecular Target; NCI Center for Cancer Research; National Cancer Institute; Natural History; Non-Small-Cell Lung Carcinoma; Oncogenes; Outcome; Pathology; Pathway interactions; Patients; Pediatric Oncology; Performance; Phase; Phase I Clinical Trials; Phase I/II Trial; Phase II Clinical Trials; Phototoxicity; Platinum; Pontine structure; Property; Proteasome Inhibitor; Proto-Oncogene Proteins c-akt; RNA; Radiation; Radiation Oncology; Radiation therapy; Recurrence; Refractory; Renal carcinoma; Resistance; Resistance development; Risk; Serum; Services; Solid Neoplasm; Specimen; Staging; Stem cell transplant; Stem cells; Technology; Testing; Thymic Carcinoma; Thymoma; Time; Tissue Microarray; Tissue Sample; Triciribine Phosphate; Tumor Biology; Ultraviolet Rays; Unresectable; Urologic Oncology; Ursidae Family; Velcade; Vision; ZD-6474; anticancer research; base; bevacizumab; cancer genome; chemotherapy; chronic graft versus host disease; comparative genomic hybridization; drug testing; epigenomics; inhibitor/antagonist; lapatinib; laser capture microdissection; leukemia; lung small cell carcinoma; mRNA Expression; medullary thyroid carcinoma; melanoma; men; mutation carrier; next generation sequencing; phase 1 study; phase 2 study; pilot trial; programs; protocol development; pyrosequencing; research clinical testing; tool; tumor; tumorigenesis; urologic

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. 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 tissue microarrays. Importantly, the CMPC provides full bioinformatics support for all these assays.

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共同服务范式。专业人员的专业知识使我们能够从项目开始就参与其中，例如方案开发，以及检测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）和临床中心的许多分支机构合作。数十项临床合作涉及CCR的许多分支，如内科肿瘤学，皮肤病学，泌尿肿瘤学，病理学实验室，儿科肿瘤学，代谢和放射肿瘤学。这些合作的状况从初步讨论到协议制定、应计和分析以及完成。对于那些已经完成的，我们期待着参与后续研究。许多研究是临床试验，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治疗难治性、转移性或不可切除实体瘤患者的研究; Pan-HER抑制剂PF-00299804治疗非小细胞肺癌的研究; R1507 II期研究的全组生物学和建库研究;在既往接受过铂类药物治疗的复发性或转移性不可切除胸腺瘤或胸腺癌患者中进行的贝利司他II期研究-含化疗;凡德他尼I/II期试验（ZD 6474 Zactima）在儿童和青少年遗传性甲状腺髓样癌中的应用;儿童脑桥胶质瘤中基因组畸变的鉴定; AKT抑制剂磷酸曲西立滨一水合物和厄洛替尼（Tarceva）的I期研究在对表皮生长因子受体（EGFR）抑制剂耐药或未经治疗的晚期肺癌或其他实体瘤受试者中;在ERBB 4突变携带者的IV期黑色素瘤患者中进行拉帕替尼治疗的II期试验; ZD 6474的靶向I期试验（凡德他尼AZCTIMA）联合蛋白酶体抑制剂硼替佐米（万珂）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）;临床GIST基因突变的临床鉴定;胰腺癌的基因型定向抗MAPK通路治疗;生殖系肾癌基因的基因组检测;晚期非小细胞肺癌、小细胞肺癌和胸腺癌的分子特征分析和靶向治疗的初步试验。然而，其他研究更侧重于了解特定疾病的潜在病理学，而不是直接测试疗法。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;接受干细胞移植的慢性移植物抗宿主病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和分子基础;从活检证实或疑似恶性疾病患者中收集血清和组织样本;滤泡性淋巴瘤的大规模甲基化分析;小细胞肺癌的分子谱;胸腺瘤亚群的分子谱;白血病生物学研究;中国食管癌;前列腺癌微环境的激光捕获显微切割和评价;毛细胞白血病患者的免疫毒素耐药性;了解来自胶质母细胞瘤的胶质瘤干细胞中的甲基化变化和亚型;甲状腺髓样癌的自然史，特别是MEN 2患者，以及参与肿瘤发生和靶向治疗耐药性发展的分子途径;非洲裔美国人和欧洲裔美国人乳腺肿瘤中全球DNA甲基化的分析;检查家族性慢性淋巴细胞白血病和单克隆B细胞淋巴细胞增多症风险之间的关系;以及胃肠道癌接受放射治疗患者的生物标志物和放射副作用。为了支持这些研究，CMPC拥有许多分子技术的专业知识，用于分析人类样本的DNA和RNA。在广泛的先进平台上发现的最先进的测定包括：DNA测序（桑格和下一代测序）、mRNA表达分析（微阵列、实时PCR、基于珠粒的）、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。