A5012759462- Fibroblast Growth Factor Research
- Cancer Genomics and Diagnostics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Metastasis and carcinoma case studies
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Kruppel-like factors research
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Lung Cancer Treatments and Mutations
- Eosinophilic Disorders and Syndromes
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- TGF-β signaling in diseases
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- IgG4-Related and Inflammatory Diseases
- Neuroendocrine Tumor Research Advances
- Genomics and Phylogenetic Studies
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Cancer-related molecular mechanisms research
- Cancer-related Molecular Pathways
The Ohio State University
2016-2025
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2018-2025
The Ohio State University Wexner Medical Center
2019-2023
Ohio University
2022
Microsatellite instability (MSI) is a pattern of hypermutation that occurs at genomic microsatellites and caused by defects in the mismatch repair system. Mismatch deficiency leads to MSI has been well described several types human cancer, most frequently colorectal, endometrial, gastric adenocarcinomas. known be both predictive prognostic, especially colorectal cancer; however, current clinical guidelines only recommend testing for endometrial cancers. Therefore, less about prevalence...
// Esko A. Kautto 1 , Russell Bonneville Jharna Miya Lianbo Yu 2 Melanie Krook Julie W. Reeser and Sameek Roychowdhury 1,3 Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA Department of Biomedical Informatics, 3 Division Medical Oncology, Internal Medicine, Correspondence to: Roychowdhury, email: Keywords : microsatellite instability, computational biology, next-generation sequencing Received November 24, 2016 Accepted December 02, Published 12, Abstract In current...
Next-generation sequencing has aided characterization of genomic variation. While whole-genome may capture all possible mutations, whole-exome remains cost-effective and captures most phenotype-altering mutations. Initial strategies for exome enrichment utilized a hybridization-based approach. Recently, amplicon-based methods were designed to simplify preparation utilize smaller DNA inputs. We evaluated two hybridization capture-based approaches, utilizing both Illumina Ion Torrent...
Abstract The fibroblast growth factor receptor (FGFR) signaling pathway is aberrantly activated in approximately 15% to 20% of patients with intrahepatic cholangiocarcinoma. Currently, several FGFR kinase inhibitors are being assessed clinical trials for FGFR-altered Despite evidence initial responses and disease control, virtually all eventually develop acquired resistance. Thus, there a critical need the development innovative therapeutic strategies overcome drug Here, we present findings...
Cholangiocarcinoma is a highly aggressive and lethal malignancy, with limited treatment options available. Recently, FGFR inhibitors have been developed utilized in FGFR-mutant cholangiocarcinoma; however, resistance often develops the genomic determinants of are not fully characterized. We completed whole-exome sequencing (WES) 11 unique tumor samples obtained from rapid research autopsy on patient FGFR-fusion-positive cholangiocarcinoma who initially responded to pan-FGFR inhibitor,...
Abstract Activation of FGFR signaling through mutations, amplifications, or fusions involving FGFR1, 2, 3, 4 is seen in multiple tumors, including lung, bladder, and cholangiocarcinoma. Currently, several clinical trials are evaluating the role novel inhibitors solid tumors. As we move forward with clinically, anticipate emergence resistance treatment. Consequently, sought to study mechanism(s) acquired using annotated cancer cell lines. We identified lines that have activating mutations 3...
Targeted, capture-based DNA sequencing is a cost-effective method to focus on coding region or other customized of the genome. There are multiple targeted methods available, but none has been systematically investigated and compared. We evaluated four commercially available custom-targeted technologies for next-generation with respect on-target sequencing, uniformity, ability detect single-nucleotide variations (SNVs) copy number variations. The that used sonication fragmentation displayed...
Background: Inactivation of DNA mismatch repair (MMR) and the resulting microsatellite instability (MSI) are frequently observed in endometrial, stomach, colorectal cancers, as well more rarely other solid tumor types. The prevalence MSI thyroid cancer has not been explored depth, although recent studies utilizing data from large sequencing efforts such Cancer Genome Atlas indicate that is absent or at least very rare most common studied histologic subtype, papillary carcinoma. This study...
TPS645 Background: Unresectable biliary tract cancer (BTC) has a poor prognosis. Frontline chemo-immunotherapy (C-IO) for advanced BTC leads to ~25% overall survival (OS) at 24-month, but 93-99% of patients reported adverse events (AEs), and 13-19% stopped treatment drugs due AEs. FGFR kinase inhibitors (FGFRi) are second-line therapy 10% with FGFR2 fusions. However, clinical trials upfront FGFRi have not accrued well. Cumulative toxicities frequently interrupt limit feasibility concurrent...
Objectives/Goals: Personalized cancer therapy based on genomic testing is advancing patient care. Genomic alterations in fibroblast growth factor receptor (FGFR) predict response to FGFR inhibitors; however, the role of RNA expression and protein activation not known. We propose examine phospho-proteomic signature FGFR-altered cancers identify new candidates for FGFR-targeted therapies. Methods/Study Population: In our preliminary study, we have curated a cohort FGFR2 mutants (13...
Abstract Metastatic breast cancer (MBC) remains a therapeutic challenge due to the persistence of minimal residual disease (MRD) and tumor recurrence. Herein we utilize model MBC that is sensitive inhibition fibroblast growth factor receptor (FGFR), resulting in robust regression pulmonary lesions upon treatment with FGFR inhibitor pemigatinib. Assessment remaining MRD revealed upregulation platelet-derived (PDGFR). Functionally, demonstrate increased response PDGF ligand stimulation...
Mutations in the RAS/RAF/MEK/ERK pathway leading to constitutive activation and uncontrolled cellular growth have been identified various human malignancies, making this a target for potential therapeutics. The activating BRAFV600E mutation is one well-characterized oncogenic that has described targeted with clinical success including melanoma hairy cell leukemia. Although BRAF-directed treatments yielded benefit subset of tumor types, such as melanoma, thyroid cancer, lung BRAF inhibition...
Relapsed SCLC is characterized by therapeutic resistance and high mortality rate. Despite decades of research, mechanisms responsible for have remained elusive owing to limited tissues available molecular studies. Thus, an unmet need remains characterization relapsed facilitate development effective therapies.We performed whole-exome transcriptome sequencing metastatic tumor samples procured from research autopsies five patients with SCLC. We implemented bioinformatics tools infer subclonal...
RNA sequencing (RNAseq) is a versatile method that can be utilized to detect and characterize gene expression, mutations, fusions, noncoding RNAs. Standard RNAseq requires 30 - 100 million reads include multiple products such as mRNA We demonstrate how targeted (capture) permits focused study on selected using desktop sequencer. capture unannotated, low, or transiently expressed transcripts may otherwise missed traditional methods. Here we describe the extraction of from cell lines,...
3620 Background: Activating genomic alterations (GAs) in the fibroblast growth factor receptor (FGFR) gene family occur many tumor types. FGFR1-3 mutations and rearrangements are of particular interest given evidence clinical activity selective FGFR inhibitors patients (pts) with susceptible alterations. We queried GAs patient samples analyzed using comprehensive profiling (CGP) performed vitro characterization select novel Methods: Tumor were assayed by hybrid capture based CGP on 0.8-1.2...
Abstract Objectives: Here we describe the durable clinical outcomes of four FGFR2 fusion positive pancreatic cancer patients treated with FGFR inhibitors as well a specific analysis alterations through our collaboration Foundation Medicine, Inc. (FMI). Methods: We identified metastatic tumor RNAseq (OSU-SpARKFuse) which identifies gene fusions from cell free DNA (cfDNA). assessed two markers (Ca19-9 and FGFRDx, an FGFR-focused liquid biopsy assay) various (Best overall response, duration,...
Abstract Genomic alterations in fibroblast growth factor receptor ( FGFR) genes are present a small number of metastatic pancreatic ductal adenocarcinomas (PDAC) and may represent an emerging subgroup patients likely to benefit from FGFR targeted therapies. Here we four FGFR2 fusion-positive PDAC who exhibited durable responses or disease control kinase inhibitors. Utilizing our custom focused cell-free DNA assay, FGFR-Dx, serially monitored variant allele fractions fusions during inhibitor...
Coevolution of tumor cells and adjacent stromal elements is a key feature during progression; however, the precise regulatory mechanisms this process remain unknown. Here, we show p53 loss enhances oncogenic KrasG12D, but not ErbB2, driven tumorigenesis in murine mammary epithelia. Stroma-specific deletion increases both epithelial fibroblast proliferation glands bearing KrasG12D oncogene epithelia, while concurrently increasing DNA damage and/or replication stress decreasing apoptosis...
PURPOSE Programmed cell death protein-1 (PD-1) receptor and ligand interactions are the target of immunotherapies for more than 20 cancer types. Biomarkers that predict response to immunotherapy microsatellite instability, tumor mutational burden, programmed ligand-1 (PD-L1) immunohistochemistry. Structural variations (SVs) in PD-L1 ( CD274) PD-L2 PDCD1LG2) have been observed cancer, but comprehensive landscape is unknown. Here, we describe genomic SVs, their potential impact on...