A5030179640- DNA Repair Mechanisms
- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- Carcinogens and Genotoxicity Assessment
- Breast Cancer Treatment Studies
- Toxin Mechanisms and Immunotoxins
- Gene expression and cancer classification
- Monoclonal and Polyclonal Antibodies Research
- Genetic factors in colorectal cancer
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Lung Cancer Research Studies
- Neuroendocrine Tumor Research Advances
- DNA and Nucleic Acid Chemistry
- Immune Cell Function and Interaction
Thomas Jefferson University
2017-2025
Sidney Kimmel Cancer Center
2017-2023
Thomas Jefferson University Hospital
2023
Harvard University
2001-2018
Dana-Farber Cancer Institute
2009-2018
Beth Israel Deaconess Medical Center
2012-2018
National Institutes of Health
2013
Brigham and Women's Hospital
2001-2012
Technical University of Denmark
2010-2012
Fox Chase Cancer Center
2012
PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As DNA cross-linking agent, cisplatin may be effective treatment hereditary BRCA1-mutated cancers. Because sporadic triple-negative (TNBC) and BRCA1-associated share features suggesting common pathogenesis, we conducted neoadjuvant trial of in TNBC explored specific biomarkers to identify predictors response. PATIENTS AND METHODS Twenty-eight women with stage II or III cancers lacking estrogen...
BRCA1/2-mutated and some sporadic triple-negative breast cancers (TNBC) have DNA repair defects are sensitive to DNA-damaging therapeutics. Recently, three independent DNA-based measures of genomic instability were developed on the basis loss heterozygosity (LOH), telomeric allelic imbalance (TAI), large-scale state transitions (LST).We assessed a combined homologous recombination deficiency (HRD) score, an unweighted sum LOH, TAI, LST scores, in neoadjuvant TNBC trials platinum-containing...
DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact can avoid the accumulation genome damage during growth and also platinum-induced damage. We sought genomic signatures indicative defective in cell lines tumors correlated these platinum sensitivity. The number subchromosomal regions allelic imbalance extending telomere (N(tAI)) predicted cisplatin vitro pathologic response preoperative treatment patients...
We have examined the regulatory role of individual components immunoglobulin antigen receptor in B-cell development by transgenic complementation Rag-1 deficient (Rag-1-) mice. Complementation with a membrane mu heavy chain (mu HC) gene allows progression developmentally arrested Rag-1- pro-B-cells to small pre-B cell stage, whereas introduction independently integrated HC and kappa light (kappa LC) transgenes promotes appearance peripheral lymphocytes which, however, remain unresponsive...
Ovarian and triple-negative breast cancers with BRCA1 or BRCA2 loss are highly sensitive to treatment PARP inhibitors platinum-based cytotoxic agents show an accumulation of genomic scars in the form gross DNA copy number aberrations. Cancers without but similar also increased sensitivity chemotherapy. Therefore, reliable biomarkers identify repair-deficient prior may be useful for directing patients platinum chemotherapy possibly inhibitors. Recently, three SNP array-based signatures...
p19ARF suppresses the growth of cells lacking p53 through an unknown mechanism. was found to complex with transcription factors E2F1, -2, and -3. Levels endogenous or ectopically expressed -3, but not E2F6, were reduced after synthesis p19ARF, a mechanism involving increased turnover. p19ARF-induced degradation E2F1 depended on functional proteasome, relocalized nucleoli when coexpressed p19ARF. Consistent levels E2F3, proliferation defective for function suppressed by effect partially...
As a probe of whether RAG-1 and RAG-2 gene products activate other genes or form part the recombinase itself, certain mutants RAG were assayed for their ability to variable-diversity-joining region [V(D)J] recombination in plasmid substrate fibroblasts. The results indicate that N-terminal one-third RAG-1, including zinc-finger-like domain, an acidic domain are dispensable activating V(D)J fibroblast, although they contribute quantitatively. In contrast, deletion C-terminal segment which has...
Abstract An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified methyl cytosine-guanine dinucleotide (CpG) binding protein 2 (MECP2) as a novel oncogene. MECP2 resides in region of the X-chromosome is significantly amplified across 18% cancers, and many cell lines have amplified, are dependent on expression growth. copy-number gain RAS family member alterations mutually exclusive several types. The splicing isoforms activate major factor...
BackgroundPlatinum-based therapy is an effective treatment for a subset of triple-negative breast cancer and ovarian patients. In order to increase response rate decrease unnecessary use, robust biomarkers that predict are needed.Patients methodsWe performed integrated genomic approach combining differential analysis gene expression DNA copy number in sensitive compared with resistant cancers two independent neoadjuvant cisplatin-treated cohorts. Functional relevance significant hits was...
Sporadic basal-like cancers (BLCs) are a common subtype of breast cancer that share multiple biological properties with BRCA1-mutated tumors. Despite being BRCA1(+/+), sporadic BLCs widely viewed as phenocopies cancers, because they hypothesized to manifest BRCA1 functional defect or breakdown pathway(s) in which plays major role. The role the repair double-strand DNA breaks by homologous recombination (HR) is its best understood function and most often implicated suppression. Therefore, it...