A5061310592- Cancer Genomics and Diagnostics
- Gastrointestinal Tumor Research and Treatment
- Sarcoma Diagnosis and Treatment
- Breast Lesions and Carcinomas
- Prostate Cancer Treatment and Research
- Mast cells and histamine
- Immune Cell Function and Interaction
- Gastrointestinal disorders and treatments
- Cytokine Signaling Pathways and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Breast Cancer Treatment Studies
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- Neurofibromatosis and Schwannoma Cases
- Biochemical and Molecular Research
- Genomics and Rare Diseases
- Gastric Cancer Management and Outcomes
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Eosinophilic Disorders and Syndromes
- Cutaneous Melanoma Detection and Management
- Cancer and Skin Lesions
- Cancer, Lipids, and Metabolism
- Cancer-related Molecular Pathways
- Melanoma and MAPK Pathways
Oregon Health & Science University
2010-2023
Portland VA Medical Center
2009-2019
OHSU Knight Cancer Institute
2009-2019
VA Portland Health Care System
2019
National Cancer Institute
2015
Dana-Farber Brigham Cancer Center
2013
Brigham and Women's Hospital
2013
Massachusetts General Hospital
2013
Seattle Cancer Care Alliance
2013
University of Washington
2013
Abstract Purpose: We recently identified a KIT exon 11 mutation in an anorectal melanoma of patient who had excellent response to treatment with imatinib. To determine the frequency mutations across subtypes, we surveyed large series tumors. Experimental Design: One hundred eighty-nine melanomas were screened for exons 11, 13, and 17. copy number was assessed by quantitative PCR. A subset cases evaluated BRAF NRAS mutations. Immunohistochemistry done assess (CD117) expression. Results:...
Amplifications and mutations in the KIT proto-oncogene subsets of melanomas provide therapeutic opportunities.We conducted a multicenter phase II trial imatinib metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with amplifications and/or mutations. Patients received 400 mg once per day twice if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening performed by mass spectroscopy.Twenty-five...
We conducted a basket clinical trial to assess the feasibility of such design strategy and independently evaluate effects multiple targeted agents against specific molecular aberrations in histologic subtypes concurrently.We enrolled patients with advanced non-small-cell lung cancer (NSCLC), small-cell cancer, thymic malignancies who underwent genomic characterization oncogenic drivers. Patients were onto not-otherwise-specified arm treated standard-of-care therapies or one following five...
Activating oncogenic mutations of BRAF have been described in patients with gastrointestinal stromal tumor (GIST), but treatment GIST inhibitors and mechanisms mediating the emergence resistance not reported. Dabrafenib is a potent ATP-competitive inhibitor kinase highly selective for mutant panel screening, cell lines, xenografts. We report prolonged antitumor activity first patient V600E BRAF-mutated who was treated inhibitor. Whole exome sequencing performed tissue obtained at time...
Clonal expansion of antigen-reactive T lymphocytes is driven by the lymphokine interleukin 2 (IL-2). To further elucidate mechanisms IL-2 action, we have utilized a differential hybridization procedure to clone IL-2-induced immediate-early genes from an IL-2-stimulated human T-cell cDNA library. increase frequency transcripts represented in library, protein synthesis inhibitor cycloheximide was included during 2-hr stimulation superinduce gene expression, and uridine analogue 4-thiouridine...
Abstract The activation of Janus protein tyrosine kinases (Jak) and STAT (signal transducer activator transcription) proteins has recently been linked to the signal transduction mechanism several cytokines. IL‐7 was observed induce a rapid dose‐dependent phosphorylation Jak 1 3 concomitantly, DNA binding activity multiple proteins. utilized by were identical those induced IL‐2 could be identified as various 5 isoforms. Moreover, induction both 3, strongly correlated with growth‐promoting...
There is an immediate and critical need for a rapid, broad-based genotyping method that can evaluate multiple mutations simultaneously in clinical cancer specimens identify patients most likely to benefit from targeted agents now use or late-stage development. We have implemented prospective approach characterize the frequency spectrum of amenable drug targeting present urothelial, colorectal, endometrioid, thyroid carcinomas melanoma. Cancer were enrolled Personalized Medicine Registry...
The interleukin 2 receptor ␣-chain (IL-2R␣) gene is a key regulator of lymphocyte proliferation.IL-2R␣ rapidly and potently induced in T cells response to mitogenic stimuli.Interleukin (IL-2) stimulates IL-2R␣ transcription, thereby amplifying expression its own high-affinity receptor.IL-2R␣ transcription at least part controlled by two positive regulatory regions, PRRI PRRII.PRRI an inducible proximal enhancer, located between nucleotides ؊276 ؊244, which contains NF-B SRE/CArG motifs.PRRII...
Abstract The newly recognized regulators of G protein signaling (RGS) attenuate heterotrimeric pathways. We have cloned an IL-2-induced gene from human T cells, cytokine-responsive 1, which encodes a member the RGS family, RGS16. RGS16 binds Giα and Gqα proteins present in inhibits Gi- Gq-mediated By comparison, mitogen-induced RGS2 Gq but not Gi signaling. Moreover, two genes exhibit marked differences expression patterns. cells is suppressed by elevated cAMP, whereas shows reciprocal...
Abstract High-throughput sequencing promises to accelerate the discovery of sequence variants, but distinguishing oncogenic mutations from irrelevant “passenger” remains a major challenge. Here we present an analysis two variants MET receptor (hepatocyte growth factor receptor) R970C and T992I (also designated R988C T1010I). Previous reports indicated that these are transforming contribute oncogenesis. We screened patients with chronic lymphocytic leukemia (CLL), acute myeloid (AML),...
Abstract KIT , PDGFRA NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), additional genetic alterations required for progression to malignancy. The most frequent secondary alteration, demonstrated ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating the MAX gene 16 76 GISTs (21%). We find 17% 50% sporadic NF1-syndromic respectively, loss protein expression 48% 90% three eight...
Primary neuroendocrine carcinoma of the breast is a rare variant, accounting for only 2% to 5% diagnosed cancers, and may have relatively aggressive behavior. Mutational profiling invasive ductal cancers has yielded potential targets directed cancer therapy, yet most studies not included carcinomas. In tissue microarray screen, we found 2.4% prevalence (9/372) carcinoma, including several with lobular morphology. We then screened primary or metastatic carcinomas (excluding papillary...