Molecular Mechanisms of Cancer Development

及时研究基因在正常生物学和癌症中的重要性的机会，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临床研究人员的合作(通常作为临床方案的联合调查人员)，参与整个NIH的合作研究项目，并作为国际合作努力的一部分。CPS成为LP部门计划的重要贡献者，并在几个研究领域取得了重大进展：国家癌症研究所胸科和胃肠道肿瘤学分会Uday an Guha。C-met扩增和RET重排在NSCLC疾病进展和获得性耐药中的作用临床研究项目包括评估ALK基因重排、HER2/Neu基因扩增在晚期非小细胞肺癌(NSCLC)患者中的作用。支持入选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病理实验室血液病理科研究员。碱性磷酸酶阳性组织细胞增生症的分子研究。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图谱。组织细胞肉瘤的完整外显子组和转录组测序显示复发性RAS通路改变。使用基因特异性FISH分析对测序数据(CNV)进行验证。弗雷德里克·巴尔，LP，CCR。与儿科横纹肌肉瘤(RMS)相关的研究项目，对涉及染色体12q和13q上的扩增的候选基因进行分析(2011年至今)。本课题致力于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内扩增的基因区域，以确定儿童横纹肌肉瘤的主要驱动基因。此外，我们一直在与巴尔博士合作研究NCOA2易位在婴儿横纹肌肉瘤发病机制中的作用，此前有报道称，在12个月以下的婴儿中发现了这种基因重排。大卫·莱文斯，LP和苏珊·麦凯姆，CDBL，CCR。C-Myc基因在小鼠模型中的扩增和表达分析，具有可诱导的亚形态myc等位基因，挽救c-Myc在肿瘤形成中的致瘤作用。Mark Raffeld，LP，CCR。以扩增MYCN癌基因为驱动因素的侵袭性后颅窝室管膜瘤新亚型的研究Armando Filie，LP，CCR。检测胸腔积液细胞学标本中BAP1和p16基因缺失情况，为鉴别良、恶性间皮瘤提供细胞学诊断指标。拉菲特·哈桑，TGMB，CCR。恶性间皮瘤患者ALK基因改变与TGMB、Ccr肺癌Arun Rajan、TGMB、Ccr的c-met与获得性耐药胸腺恶性肿瘤和非小细胞肺癌。孟浩英，VB，CCR。不同癌症类型的HER2基因扩增检测以确定AdHER2 DC疫苗(NCI方案)的适合性和应答性

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)