Molecular Mechanisms of Cancer Development

癌症发展的分子机制

• 批准号: 10262779
• 负责人: Svetlana Pack
• 金额: $ 12.98万
• 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/10262779
• 关键词: 12q; 13q; ALK gene; Age-Months; Alleles; BAP1 gene; Benign; Biology; CDKN2A gene; Candidate Disease Gene; Chest; Childhood Rhabdomyosarcoma; Chromosomes; Clinical Investigator; Clinical Protocols; Clinical Research; Collaborations; Cytology; Cytopathology; Data; Development; Disease Progression; ERBB2 gene; Eligibility Determination; Enrollment; Ependymoma; Evaluation; Event; FGFR1 gene; Fluorescent in Situ Hybridization; Fossa; Gene Amplification; Gene Deletion; Gene Mutation; Gene Rearrangement; Genes; Hematopathology; Histiocytic sarcoma; Histiocytosis; IRF4 gene; Infant; International; Investigation; Laboratories; Lymphoma; MYCN gene; Malignant Neoplasms; Malignant mesothelioma; Malignant neoplasm of lung; Molecular; Molecular Cytogenetics; Molecular Profiling; NCI Center for Cancer Research; NCOA2 gene; National Cancer Institute; Non-Small-Cell Lung Carcinoma; Oncogene Activation; Oncogenes; Oncology; PDGFRA gene; PIK3CA gene; Pathogenesis; Pathology; Pathway interactions; Patients; Pediatric Oncology; Pleural effusion disorder; Process; Protocols documentation; Recording of previous events; Recurrence; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Resistance; Rhabdomyosarcoma; Role; Sampling; Testing; Thymus Gland; Time; United States National Institutes of Health; Vaccines; Validation; c-myc Genes; cancer type; diagnostic biomarker; exome sequencing; infancy; interest; mouse model; novel; programs; response; therapy resistant; transcriptome sequencing; tumor; tumor progression; tumorigenic

The opportunity to pursue the importance of the genes in normal biology and cancer in a timely manner hinged decisively on developing more refined and broader understandings of the events associated with aberrant activation of oncogenes and silence of the tumor-repressor genes during cancer formation. The CPS staff actively participates in collaborations with CCR clinical investigators (often as co-investigators on clinical protocols), in collaborative research projects across the NIH and as a part of international collaborative efforts. The CPS became an important contributor to the programs of the LP sections and has made significant progress in several lines of investigation: Udayan Guha, Thoracic & GI Oncology Branch at National Cancer Institute. Role of c-MET amplification and RET rearrangement in disease progression and acquired resistance to therapy in NSCLC Clinical research projects included evaluation of ALK gene rearrangements, HER2/Neu gene amplification in patients with advanced non-small cell lung cancer (NSCLC). Supported molecular characterizations of enrolled patients for protocol and treatment eligibility. History of Lung Cancer: HER2, ALK, FGFR1, PIK3CA, PDGFRA FISH study. Elaine Jaffe, Hematopathology Section Research Fellows, Laboratory of Pathology, CCR. Molecular study of ALK-positive histiocytosis. Elaine Jaffe, LP, CCR, The role of IRF4 gene rearrangement in uncommon Lymphoma types. Elaine Jaffe/Mark Raffeld, LP, CCR, Molecular Profiling of Histiocytic sarcoma. Whole Exome and Transcriptome Sequencing of Histiocytic Sarcoma reveals Recurrent RAS Pathway Alterations. Validation of the Sequencing data (CNV) using gene-specific FISH assays. Frederic Barr, LP, CCR. Research projects related to pediatric Rhabdomyosarcoma (RMS) analysis for candidate genes involved in amplicons on Chromosome 12q and 13q (2011-now). This project is focused on elucidating the mechanisms of rhabdomyosarcoma tumor progression. Using FISH probes we will narrow down the amplified gene regions within12q13-14 to identify major driver genes for childhood rhabdomyosarcoma. In addition, we've been studying the role of the NCOA2 translocations in the pathogenesis of infantile rhabdomyosarcoma in collaboration with Dr. Barr following report that such gene rearrangement was identified in infants below 12 months of age. David Levens, LP and Susan Mackem, CDBL, CCR. c-Myc amplification and expression analysis of the mouse model with the inducible hypomorphic myc allele that rescues tumorigenic effect of c-Myc on tumor formation. Mark Raffeld, LP, CCR. Investigation of the novel subtype of the aggressive Posteriior Fossa Ependymoma with amplified MYCN oncogene as a driver. Armando Filie, LP, CCR. Investigation of the BAP1 and p16 gene deletions status in pleural effusion cytology samples to potentially serve as differential diagnostic marker for benign vs malignant mesothelioma in cytopathology. Raffit Hassan, TGMB, CCR. ALK gene alterations in patients with Malignant Mesothelioma Udayan Guha, TGMB, CCR. C-MET and acquired resistance in Lung Cancer Arun Rajan, TGMB, CCR. Thymic malignancies and NSCLC. Hoyoung Maeng, VB, CCR. HER2 gene amplification testing in different cancer types to determine eligibility and response to for AdHER2 DC vaccine (NCI protocol)

及时探究基因在正常生物学和癌症中的重要性的机会决定性地取决于对癌症形成过程中癌基因异常激活和肿瘤抑制基因沉默相关事件的更精细和更广泛的理解。 CPS 工作人员积极参与与 CCR 临床研究人员（通常作为临床方案的共同研究人员）的合作、NIH 的合作研究项目以及国际合作努力的一部分。 CPS 成为 LP 部门项目的重要贡献者，并在多个研究领域取得了重大进展：Udayan Guha、国家癌症研究所胸部和胃肠道肿瘤科。 c-MET 扩增和 RET 重排在 NSCLC 疾病进展和获得性治疗耐药中的作用临床研究项目包括评估晚期非小细胞肺癌 (NSCLC) 患者的 ALK 基因重排、HER2/Neu 基因扩增。支持登记患者的方案和治疗资格的分子特征。肺癌病史：HER2、ALK、FGFR1、PIK3CA、PDGFRA FISH 研究。 Elaine Jaffe，CCR 病理学实验室血液病理学部分研究员。 ALK 阳性组织细胞增多症的分子研究。 Elaine Jaffe，LP，CCR，IRF4 基因重排在罕见淋巴瘤类型中的作用。 Elaine Jaffe/Mark Raffeld，LP，CCR，组织细胞肉瘤的分子分析。组织细胞肉瘤的全外显子组和转录组测序揭示了复发性 RAS 通路改变。使用基因特异性 FISH 检测验证测序数据 (CNV)。弗雷德里克·巴尔，LP，CCR。与儿科横纹肌肉瘤 (RMS) 分析相关的研究项目，分析涉及染色体 12q 和 13q 扩增子的候选基因（2011 年至今）。该项目的重点是阐明横纹肌肉瘤肿瘤进展的机制。使用 FISH 探针，我们将缩小 12q13-14 内扩增基因区域的范围，以确定儿童横纹肌肉瘤的主要驱动基因。此外，在有报道称在 12 个月以下的婴儿中发现了这种基因重排后，我们一直与 Barr 博士合作研究 NCOA2 易位在婴儿横纹肌肉瘤发病机制中的作用。 David Levens，LP 和 Susan Mackem，CDBL、CCR。具有可诱导的亚效型 myc 等位基因的小鼠模型的 c-Myc 扩增和表达分析，该等位基因挽救了 c-Myc 对肿瘤形成的致瘤作用。马克·拉菲尔德，LP，CCR。以扩增的 MYCN 癌基因作为驱动因素，研究侵袭性后窝室管膜瘤的新亚型。阿曼多·菲利 (Armando Filie)，LP，CCR。研究胸腔积液细胞学样本中 BAP1 和 p16 基因缺失状态，有可能作为细胞病理学中良性与恶性间皮瘤的鉴别诊断标记。拉菲特·哈桑，TGMB，CCR。恶性间皮瘤 Udayan Guha、TGMB、CCR 患者的 ALK 基因改变。肺癌 Arun Rajan、TGMB、CCR 中的 C-MET 和获得性耐药。胸腺恶性肿瘤和非小细胞肺癌。 Hoyoung Maeng，VB，CCR。对不同癌症类型进行 HER2 基因扩增测试，以确定 AdHER2 DC 疫苗的资格和反应（NCI 方案）