A5102914349- Cancer Genomics and Diagnostics
- Ovarian cancer diagnosis and treatment
- Chronic Lymphocytic Leukemia Research
- Genetic factors in colorectal cancer
- Acute Lymphoblastic Leukemia research
- Molecular Biology Techniques and Applications
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Rare Diseases
- Acute Myeloid Leukemia Research
- Biosimilars and Bioanalytical Methods
- Advanced Breast Cancer Therapies
- Biomedical and Engineering Education
- Plant Reproductive Biology
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Genomics and Phylogenetic Studies
- Lymphoma Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Soft tissue tumor case studies
- Photosynthetic Processes and Mechanisms
Bristol-Myers Squibb (United States)
2021-2024
Human Genome Sciences (United States)
2018-2022
Johns Hopkins University
2015-2020
Sidney Kimmel Comprehensive Cancer Center
2015-2020
Hospital for Sick Children
2012-2016
University of Toronto
2012-2016
Noninvasive liquid biopsy analysis of circulating tumor DNA permits direct detection early-stage cancers.
High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of cancer and has a poor outcome. It been proposed that fallopian tube cancers may be precursors HGSOC but evolutionary evidence for this hypothesis limited. Here, we perform whole-exome sequence copy number analyses laser capture microdissected lesions (p53 signatures, tubal intraepithelial carcinomas (STICs), carcinomas), cancers, metastases from nine patients. The majority tumor-specific alterations in were present...
Massively parallel sequencing approaches are beginning to be used clinically characterize individual patient tumors and select therapies based on the identified mutations. A major question in these analyses is extent which methods identify actionable alterations whether examination of tumor tissue alone sufficient or matched normal DNA should also analyzed accurately tumor-specific (somatic) alterations. To address issues, we comprehensively evaluated 815 tumor-normal paired samples from...
Abstract Purpose: Ovarian cancer is the leading cause of death from gynecologic malignancy in United States, with high rates recurrence and eventual resistance to cytotoxic chemotherapy. Model systems that allow for accurate reproducible target discovery validation are needed support further drug development this disease. Experimental Design: Clinically annotated patient-derived xenograft (PDX) models were generated tumor cells isolated ascites or pleural fluid patients undergoing clinical...
Abstract Intraductal papillary mucinous neoplasms (IPMNs) and cystic (MCNs) are non-invasive that often observed in association with invasive pancreatic cancers, but their origins evolutionary relationships poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, small associated carcinomas 18 patients using whole exome or targeted sequencing. Using analyses, establish both IPMNs MCNs direct precursors to cancer. Mutations SMAD4 TGFBR2 frequently restricted carcinoma, while...
A machine learning approach to detect somatic mutations in cancer patients outperforms existing methods and may improve clinical outcome.
To improve our understanding of ovarian cancer, we performed genome-wide analyses 45 cancer cell lines. Given the challenges genomic tumors without matched normal samples, developed approaches for detection somatic sequence and structural changes integrated these with epigenetic expression alterations. Alterations not previously implicated in included amplification or overexpression ASXL1 H3F3B, deletion underexpression CDC73 TGF-beta receptor pathway members, rearrangements YAP1-MAML2...
Abstract Background Characterization of circulating tumor DNA (ctDNA) has been integrated into clinical practice. Although labs have standardized validation procedures to develop single locus tests, the efficacy on-site plasma-based next-generation sequencing (NGS) assays still needs be proved. Materials and Methods In this retrospective study, we profiled from matched tissue plasma samples 75 patients with cancer. We applied an NGS test that detects clinically relevant alterations in 33...
The lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared examination 505 cancer-related genes. Independent analyses clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, PCR-based methods reveals a positive percent agreement >97%. We observe high concordance...
7501 Background: In patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based regimens, achieving CR current treatment is uncommon. New therapies achieve deep durable responses are needed. We report the primary analysis of phase 1/2, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) study evaluating liso-cel in pts CLL/SLL. Methods: Pts must have received at least 2 prior lines therapy, including a BTKi. Eligible target dose either 50 (DL1) or 100 (DL2)...
1529 Background: The anticipated widespread adoption of large scale genomic analyses in precision oncology mandates the development a gene actionability framework. Previous efforts clinical interpretation alterations mainly rely on expert opinion and manual curation primary literature. Furthermore, analytic challenges such as distinguishing somatic -driver- mutations from germline have limited information. Methods: We comprehensively evaluated 815 tumor-normal paired samples 15 tumor types...
During V(D)J recombination of immunoglobulin genes, p53 and nonhomologous end-joining (NHEJ) suppress aberrant rejoining DNA double-strand breaks induced by recombinase-activating genes (Rags)-1/2, thus maintaining genomic stability limiting malignant transformation during B-cell development. However, Rag deficiency does not prevent leukemogenesis in p53/NHEJ mutant mice, revealing that NHEJ also Rag-independent mechanisms leukemogenesis. Using several cytogenomic approaches, we identified a...
<h3>Background</h3> CLL is an incurable hematologic malignancy characterized by progressive accumulation of clonally derived CD19+ B-cell lymphocytes. CAR T cell therapies are promising treatments but inherent dysfunction has limited their development in CLL. Preclinical studies suggest ibrutinib may modulate cells directly to improve function independently antitumor effects. Liso-cel autologous, CD19-directed, defined composition, 4–1BB product administered at equal target doses CD8+ and...
Abstract Massively parallel sequencing approaches are beginning to be used clinically characterize individual patient tumors and identify targeted therapies based on mutations identified. A major question in these analyses is the extent which methods actionable alterations patients whether examination of tumor tissue alone sufficient or matched normal DNA should also analyzed accurately tumor-specific (somatic) alterations. To address issues, we comprehensively evaluated tumor-normal paired...
<p>Table S4: Somatic Sequence Alterations in parental tumor and xenograft DF101</p>
<p>Table S1: Optimal conditions for PDX luciferization; Table S3: BROCA characterization; S6: PIK3CA FISH. Figure Schema generation; Figures S2: IHC of DF68; Array CGH DF86; S4: PI3K pathway analysis from RPPA; S5: Correlation between BLI and plasma CA125</p>