A5018521696- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- BRCA gene mutations in cancer
- Cancer Cells and Metastasis
- Breast Cancer Treatment Studies
- Lung Cancer Treatments and Mutations
- Gene expression and cancer classification
- HER2/EGFR in Cancer Research
- Advanced biosensing and bioanalysis techniques
- Nutrition, Genetics, and Disease
- Cancer-related Molecular Pathways
- IL-33, ST2, and ILC Pathways
- Advanced Biosensing Techniques and Applications
- Genomics and Chromatin Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Advanced Breast Cancer Therapies
- Molecular Biology Techniques and Applications
- Cytokine Signaling Pathways and Interactions
- Ferrocene Chemistry and Applications
- Genetic factors in colorectal cancer
- DNA and Nucleic Acid Chemistry
- Neurogenetic and Muscular Disorders Research
- Genetics, Bioinformatics, and Biomedical Research
- Epigenetics and DNA Methylation
- Radiopharmaceutical Chemistry and Applications
University of Pittsburgh
2015-2024
University of Isfahan
2024
Magee-Womens Research Institute
2015-2023
UPMC Hillman Cancer Center
2015-2023
Isfahan University of Medical Sciences
2018-2023
Cancer Research Center
2014-2022
Alzahra Medical and Education Center
2022
Alzahra University
2022
Leiden University Medical Center
2022
Central South University
2019
Given the clinical relevance of ESR1 mutations as potential drivers resistance to endocrine therapy, this study used sensitive detection methods determine frequency in primary and metastatic breast cancer, cell-free DNA (cfDNA).Six (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits 0.05% 0.16%, tumors (n = 43), bone 12) brain metastases 38), cfDNA 29). Correlations between lesions single (1 patient) or serial blood draws (4 patients)...
Mutations in the estrogen receptor alpha (ERα) 1 gene (ESR1) are frequently detected ER+ metastatic breast cancer, and there is increasing evidence that these mutations confer endocrine resistance cancer patients with advanced disease. However, their functional role not well-understood, at least part due to a lack of ESR1 mutant models. Here, we describe generation characterization genome-edited T47D MCF7 cell lines two most common mutations, Y537S D538G. Genome editing was performed using...
Invasive lobular carcinoma (ILC) is a histologic subtype of breast cancer that frequently associated with favorable outcomes, as approximately 90% ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest patients receiving adjuvant endocrine therapy may not benefit much invasive ductal carcinoma. On basis these observations, we characterized ER function and response in models. The ER-positive cell lines MDA MB 134VI (MM134) SUM44PE were used to examine...
BackgroundEstrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent fusion proteins yet be identified in advanced cancer.Patients and methodsTo identify genomic structural rearrangements (REs) including gene fusions acquired we undertook a multimodal sequencing effort three patient cohorts: (i) mate-pair and/or RNAseq 6...
Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these are known as mediators endocrine resistance, their potential role promoting disease has not yet mechanistically addressed. In this study, we show the presence ESR1 exclusively distant but local recurrences five independent cancer cohorts. concordance with transcriptomic profiling ESR1-mutant tumors, genome-edited Y537S and D538G-mutant...
Abstract Estrogen receptor alpha (ER/ ESR1 ) is frequently mutated in endocrine resistant ER-positive (ER+) breast cancer and linked to ligand-independent growth metastasis. Despite the distinct clinical features of mutations, their role intrinsic subtype switching remains largely unknown. Here we find that mutant cells samples show a significant enrichment basal markers, six cytokeratins (BCKs) are most enriched genes. Induction BCKs independent ER binding instead associated with chromatin...
Increased evidence suggests that somatic mutations in the ligand-binding domain of estrogen receptor [ER (ERα/ESR1)] are critical mediators endocrine-resistant breast cancer progression. Insulinlike growth factor-1 (IGF1) is an essential regulator development and tumorigenesis also has a role endocrine resistance. A recent study showed enhanced crosstalk between IGF1 ERα ESR1 mutant cells, but detailed mechanisms incompletely understood. Using genome-edited MCF-7 T47D cell lines harboring...
Breast cancer is the most common invasive among women worldwide. Next-generation sequencing (NGS) has revolutionized study of across research labs around globe; however, genomic testing in clinical settings remains limited. Advances reliability, pipeline analysis, accumulation relevant data, and reduction costs are rapidly increasing feasibility NGS-based decision making.We report development MammaSeq, a breast cancer-specific NGS panel, targeting 79 genes 1369 mutations, optimized for use...
DNA sequencing has identified a limited number of driver mutations in metastatic breast cancer beyond single base-pair the estrogen receptor (
<b><i>Objective:</i></b> Twenty to fifty percent of estrogen receptor-positive (ER+) metastatic breast cancers express mutations within the ER ligand-binding domain. While most studies focused on constitutive signaling activity commonly engendered by these selected during deprivation therapy, our study was aimed at investigating distinctive phenotypes conferred different this class. <b><i>Methods:</i></b> We examined two prevalent mutations,...
Autosomal dominant variants in LDB3 (also known as ZASP), encoding the PDZ-LIM domain-binding factor, have been linked to a late onset phenotype of cardiomyopathy and myofibrillar myopathy humans. However, despite knockout mice displaying much more severe with premature death, bi-allelic not yet reported. Here we identify biallelic loss-of-function five unrelated families by next-generation sequencing. In first family, identified compound heterozygous LOF fetus bilateral talipes mild left...
Abstract FLVCR1 encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. is widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, ethanolamine transport. While Flvcr1 knockout mice die utero skeletal malformations defective erythropoiesis reminiscent of Diamond-Blackfan anemia, rare biallelic pathogenic variants are linked to childhood or adult-onset...
Protein arginine methyltransferase 7 (PRMT7) is a member of family enzymes that catalyzes the methylation residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes detailed clinical characteristics this syndrome. Thus, we aim to delineate phenotypic...
Estrogen receptor (ER) activity is critical for the development and progression of majority breast cancers. It known that ER differentially bound to DNA leading transcriptomic phenotypic changes in different cancer models. We investigated whether single nucleotide variants (SNVs) binding sites (regSNVs) contribute action through cistrome, thereby affecting disease progression. Here we developed a computational pipeline identify SNVs using chromatin immunoprecipitation sequencing (ChIP-seq)...
Objective Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, frequently only few affected individuals described for each gene. Herein, we characterize large cohort of biallelic ENTPD1 , gene previously linked to 64 (Mendelian Inheritance Man # 615683). Methods Individuals variants were recruited worldwide. Deep phenotyping and molecular characterization performed....
Biallelic pathogenic variants in the genes encoding dolichol-phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- C-mannosylation, are rare causes of congenital disorders glycosylation. Pathogenic DPM1 DPM2 associated with muscle-eye-brain (MEB) disease, whereas DPM3 have mostly been reported patients isolated muscle disease-dystroglycanopathy. Thus far, only one affected individual compound heterozygous presenting...
Abstract Constitutively active estrogen receptor-α (ER/ ESR1 ) mutations have been identified in approximately one third of ER+ metastatic breast cancer. Although these are known mediators endocrine resistance, their potential role promoting disease has not yet mechanistically addressed. In this study, we show the presence exclusively distant, but local recurrences. concordance with transcriptomic profiling mutant tumors, genome-edited Y537S and D538G cell models a reprogrammed adhesive gene...
Abstract Estrogen receptor alpha (ER/ ESR1 ) is mutated in 30-40% of endocrine resistant ER-positive (ER+) breast cancer. mutations cause ligand-independent growth and increased metastasis vivo vitro . Despite the distinct clinical features changes therapeutic response associated with mutations, there are no data about their potential role intrinsic subtype switching. Applying four luminal basal gene set pairs, mutant cell models samples showed a significant enrichment markers. Among them,...