A5014498361- Cancer Genomics and Diagnostics
- BRCA gene mutations in cancer
- CRISPR and Genetic Engineering
- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Advanced Breast Cancer Therapies
- Lung Cancer Treatments and Mutations
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Chromosomal and Genetic Variations
- Single-cell and spatial transcriptomics
- DNA Repair Mechanisms
- Breast Cancer Treatment Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Bladder and Urothelial Cancer Treatments
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Renal cell carcinoma treatment
- Gastric Cancer Management and Outcomes
- Cancer Immunotherapy and Biomarkers
- Urinary and Genital Oncology Studies
- RNA Research and Splicing
Guardant (United States)
2019-2025
University of California, San Francisco
2017-2019
San Jose State University
2006
A wide range of human diseases result from haploinsufficiency, where the function one two gene copies is lost. Here, we targeted remaining functional copy a haploinsufficient using CRISPR-mediated activation (CRISPRa) in Sim1 and Mc4r heterozygous mouse models to rescue their obesity phenotype. Transgenic-based CRISPRa targeting promoter or its distant hypothalamic enhancer up-regulated expression endogenous allele tissue-specific manner, rescuing phenotype mice. To evaluate therapeutic...
Abstract Purpose: PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) BRCA1/2 mutations. Acquired reversions can restore function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, reversion mutations has not been established. Next-generation sequencing (NGS) cell-free DNA (cfDNA) provides a platform identify these three types Experimental Design: Patients...
MSI-H identified by ctDNA: prevalence across 21 advanced cancers and outcomes from >700 patients.
Abstract Background: Recent evidence suggests dynamic changes in cell-free circulating tumor DNA (ctDNA), defined as the maximum variant allele fraction (maxVAF), is predictive of overall survival (OS) colorectal cancer (CRC) patents. As such, we leverage an advanced statistical approach, joint modeling longitudinal and time-to-event data (JM), to associate ctDNA dynamics OS. Contrasting with traditional methods, a unique advantage JM results assume form patient-specific adaptive...
Abstract Introduction: Despite success of genomic tumor characterization from plasma, one challenge cell-free DNA (cfDNA) profiling is an inability to rule out the presence actionable mutations. This difficulty stems assess if known drivers are absent or level insufficient for detection in assay. Confident negative variant prediction could allow clinicians expedite clinical action cfDNA without waiting tissue biopsy sequencing when no alterations identified. Here we leverage assay which...
56 Background: Identification of MSI-H is clinically meaningful in patients with aGI given the associated approval multiple immune checkpoint inhibitors. has long been assessed via tissue analysis; and insights from plasma-based approaches are limited to small validation studies. We sought assess prevalence initial acquired status across report real-world outcomes colorectal (CRC) who received ICI after identification by a commercially available liquid biopsy (LBx) assay. Methods: Genomic...
A wide range of human diseases result from haploinsufficiency, where gene expression is decreased as compared to normal conditions. Haploinsufficiency a typical mechanism in autosomal dominant disorders. Rare mutations Sim1 or Mc4r are models haploinsufficiency causing severe early-onset obesity with hyperphagia. Gene therapy by adenovirus vectors has been developed rescue such disorders, expressing the allele place mutant. However, this strategy limited size DNA that can be packaged virus,...
Mastomys are the most widespread African rodent and carriers of various diseases such as plague or Lassa virus. In addition, mastomys have rapidly gained a large number mammary glands. Here, we generated genome, variome, transcriptomes for coucha. As diverged at similar times from mouse rat, demonstrate their utility comparative genomic tool these commonly used animal models. Furthermore, identified over 500 accelerated regions, often residing near important developmental genes within exons...
e13627 Background: The analysis of genomic variants is crucial in precision oncology research, offering insights into cancer risks and progression, especially diverse types such as lung adenocarcinoma (LUAD). However, research often grapples with balancing patient privacy the need for comprehensive, high-quality datasets. Our project addresses this by creating synthetic clinical-genomic data, which maintains confidentiality provides a rich resource research. Methods: Leveraging...
Abstract Background: Osimertinib is currently the most common precision therapy for patients with non- small cell lung cancer (NSCLC) EGFR mutations. While it prolongs progression-free survival, resistance eventually develops in many, leading to disease progression. Somatic NGS has identified mutations pathway and other oncogenes, but these account only 40-45% of cases, suggesting non-genetic factors, such as epigenetic changes, may be involved. This study investigates landscape at diagnosis...
Detecting genomic alterations (GAs) in advanced urothelial carcinoma (aUC) can expand treatment options by identifying candidates for targeted therapies. Erdafitinib is FDA-approved patients with platinum-refractory aUC activating mutation or fusion FGFR2/3. We explored the prevalence and spectrum of FGFR2/3 GAs identified plasma cfDNA NGS testing (Guardant360) 997 aUC. were detected 201 (20%) characterized 141 (14%). Our results indicate Guardant360-based GA detection rate similar to those...
Abstract Background: The CDK4/6 inhibitors (palbociclib, abemaciclib, and ribociclib) have heralded a paradigm shift in the management of people with metastatic ER+/ HER2- breast cancer. Traditionally assessment genomic status has relied on tumor testing from solid biopsy, however, circulating DNA (ctDNA) demonstrated strong concordance proving viability ctDNA as diagnostic alternative to tissue testing. Using real-world clinical-genomic dataset, we aimed describe clinical outcomes patients...
Abstract Introduction: ESR1 mutations are biological indicators of endocrine resistance observed in 20-30% patients with metastatic breast cancer treated aromatase inhibitor (AI) therapy. A number have been characterized, including single nucleotide variants codons 380, 463, 536, 537, and 538. However, not characterized using large-scale, real-world population studies. Here we describe the subclonal landscape a dataset advanced anti-estrogen Methods: The GuardantINFORM™ clinical-genomic...
Abstract Background Liquid biopsy tests capable of tumor profiling with NGS have recently received FDA approval for companion diagnostic treatment selection and profiling, demonstrating the clinical validity identification druggable variants such information. As amount cfDNA per volume plasma varies greatly from patient to patient, whole blood/plasma volumes advanced cancer patients are often limited, it would be advantageous a liquid able operate minimal input, providing robust results...
Abstract Background: The FDA recently approved alpelisib, in combination with fulvestrant, for HR+/HER2- PIK3CA-mutated advanced/metastatic breast cancer after trials demonstrated improved clinical outcomes this targeted combination. companion diagnostic, the Qiagen Therascreen, is a PCR-based kit detecting 11 single nucleotide variant (SNV) mutations limited to 3 exons PIK3CA gene. However, other functionally significant outside these hotspots, including activating SNVs and indels, have...
Abstract Background: Real-world evidence (RWE), specifically the integration of clinical and molecular data, plays an increasingly important role in elucidating landscape advanced solid tumors, at diagnosis progression, furthering precision oncology research. However, reliance on tissue genomic testing results within these RWE databases significantly limits our understanding tumor evolution as profiles are typically limited to a single time point, generally diagnosis, biopsies not routinely...
<p>Supplemental Table 1</p>
<p>Supplemental Table 1</p>
<div>AbstractPurpose:<p>PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) <i>BRCA1/2</i> mutations. Acquired reversions can restore function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, reversion mutations has not been established. Next-generation sequencing (NGS) cell-free DNA (cfDNA) provides a platform identify these three types...
<div>AbstractPurpose:<p>PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) <i>BRCA1/2</i> mutations. Acquired reversions can restore function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, reversion mutations has not been established. Next-generation sequencing (NGS) cell-free DNA (cfDNA) provides a platform identify these three types...