The Clinical Molecular Profiling Core (CMPC) is a collaborative core that seeks to go beyond the common service paradigm of other laboratory cores. The expertise of its personnel allows involvement from the start of a project, such as the protocol development, through performance of the assay and biostatistical analyses. 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/NCI) and sister centers in the NCI. The status of these collaborations range from preliminary discussions through protocol development, accrual and analysis, and completion to publication; for those that are completed, we look forward to being involved in follow up studies. Many of the studies are clinical trials testing or identifying drugs for early phase clinical trials. These include studies such as: Phase 1 study of CaboNivo or CaboNivoIp in Metastatic Urothelial and Genitourinary Cancer and A Phase II Trial of Mutation-Targeted Therapy with Sunitinib or Everolimus in Patients with Neuroendocrine tumors. In the past we have supported Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial and a trial in Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. However, other investigations are more focused on understanding the underlying pathology of specific diseases and are not directly testing a therapy. In the last year these studies included publications (4 of 8) on: Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report from the National Institutes of Health Gastrointestinal Stromal Tumor Clinic. (Boikos et al., JAMA Oncol. 2016); Neuroendocrine Tumor of the Pancreas as a Manifestation of Cowden Syndrome: A Case Report. (Neychev et al., J Clin Endocrinol Metab. 2016); Impact of Telomere Length on Survival in Classic and Variant Hairy Cell Leukemia. (Arons et al., Leuk Res. 2015); and An Integrated Prognostic Classifier for Stage I Lung Adenocarcinoma Based on mRNA, microRNA, and DNA Methylation Biomarkers. (Robles et al., J Thorac Oncol. 2015). Significantly, resources have been devoted to actualizing clinical exome sequencing using Illumina next-generation sequencing in the context of our CLIA [Clinical Laboratory Improvement Amendments] laboratory. To support these studies, the CMPC has expertise in many molecular technologies for the analysis of DNA and RNA from human specimens. Other state of the art assays utilized in the CMPC are a wide range of advanced platforms that 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC011040-09
Application #
9344159
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Grasso, Catherine S; Tang, Yujie; Truffaux, Nathalene et al. (2015) Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med 21:827
Yang, Xiaohong R; Killian, J Keith; Hammond, Sue et al. (2015) Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH) arrays. PLoS One 10:e0116078
Howard, Brandi; Wang, Yonghong; Xekouki, Paraskevi et al. (2014) Integrated analysis of genome-wide methylation and gene expression shows epigenetic regulation of CYP11B2 in aldosteronomas. J Clin Endocrinol Metab 99:E536-43
Petrini, Iacopo; Meltzer, Paul S; Kim, In-Kyu et al. (2014) A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nat Genet 46:844-9
Waterfall, Joshua J; Killian, J Keith; Meltzer, Paul S (2014) The role of mutation of metabolism-related genes in genomic hypermethylation. Biochem Biophys Res Commun 455:16-23
Azad, Nilofer; Yu, Minshu; Davidson, Ben et al. (2013) Translational predictive biomarker analysis of the phase 1b sorafenib and bevacizumab study expansion cohort. Mol Cell Proteomics 12:1621-31
Aung, Phyu P; Killian, Keith; Poropatich, Carrie O et al. (2013) Primary neuroendocrine tumors of the kidney: morphological and molecular alterations of an uncommon malignancy. Hum Pathol 44:873-80
Miettinen, Markku; Killian, Jonathan Keith; Wang, Zeng-Feng et al. (2013) Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation. Am J Surg Pathol 37:234-40
Abaan, Ogan D; Polley, Eric C; Davis, Sean R et al. (2013) The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology. Cancer Res 73:4372-82
Di, Li-Jun; Byun, Jung S; Wong, Madeline M et al. (2013) Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer. Nat Commun 4:1449

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