Molecular Profiling of Clinical Specimens

临床样本的分子分析

• 批准号: 8938454
• 负责人: Daniel Edelman
• 金额: $ 203.24万
• 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/8938454
• 关键词: Adolescent; Adult; Adverse effects; African American; Aggressive Fibromatosis; Algorithms; 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; Feasibility Studies; 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; Length; 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; Primary carcinoma of the liver cells; Property; Proteasome Inhibitor; Proto-Oncogene Proteins c-akt; RNA; Radiation; Radiation Oncology; Radiation therapy; Recurrence; Refractory; Renal carcinoma; Resistance; Resistance development; Resources; Risk; Serum; Services; Solid Neoplasm; Specimen; Staging; Stem cell transplant; Stem cells; Technology; Testing; Therapeutic; Thymic Carcinoma; Thymoma; Time; 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; exome sequencing; gamma secretase; inhibitor/antagonist; lapatinib; laser capture microdissection; leukemia; lung small cell carcinoma; mRNA Expression; medullary thyroid carcinoma; melanoma; men; mutation carrier; next generation; next generation sequencing; phase 1 study; phase 2 study; pilot trial; programs; protocol development; pyrosequencing; research clinical testing; telomere; 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. 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.

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。数十项临床协作涉及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、新陈代谢和放射肿瘤学。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；贝立诺斯特在复发或转移性不能切除的胸腺瘤或胸腺癌患者中的第二阶段研究；先前接受过含铂化疗的患者；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中的基因组异常；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抑制剂一水合三氢磷酸三氯和厄洛替尼(Tarceva)的I期研究；针对ERBB4突变携带者的IV期黑色素瘤患者的雷帕替尼治疗的II期试验；ZD6474(Vandetanib AZCTIMA)加蛋白酶体抑制剂Bortezomib(VELCADE)在成人实体瘤中的靶向I期试验，重点关注遗传性或散发性、局部晚期或转移性甲状腺癌(MTC)；临床GIST基因突变的临床鉴定；胰腺癌的基因组定向抗MAPK通路治疗；生殖系肾癌基因的基因组测试；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；接受干细胞移植的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的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；前列腺癌的激光捕获显微解剖和微环境评估；毛细胞白血病患者的免疫毒素抵抗；了解胶质母细胞瘤衍生的胶质瘤干细胞的甲基化变化和亚型；甲状腺髓样癌的自然病史，尤其是男性2患者的病史，以及参与肿瘤发生和对靶向治疗的耐药性的分子途径；分析非裔美国人和欧洲裔美国人患者乳腺肿瘤中的全球DNA甲基化；研究家族性慢性淋巴细胞白血病风险与单克隆性B细胞淋巴细胞增多症之间的联系；以及胃肠癌放射治疗患者的生物标志物和辐射副作用。去年又增加了八项合作，其中包括：波纳替尼治疗晚期或转移性甲状腺髓样癌的第二阶段研究；使用Coxen算法进行晚期尿路上皮癌患者个体化治疗敏感性预测的可行性研究；伽玛分泌酶抑制剂PF-03084014在患有韧带样瘤/侵袭性肿瘤的成年人中的第二阶段试验；以及在肝细胞癌中的端粒长度和甲基化。值得注意的是，资源已经开始用于实施使用Illumina下一代测序仪的临床外显子组测序。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。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)、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(微阵列和焦测序)、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全面的生物信息学支持。