Molecular Mechanisms of Cancer Development

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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)