A5076122477- Cancer Genomics and Diagnostics
- BRCA gene mutations in cancer
- PARP inhibition in cancer therapy
- Molecular Biology Techniques and Applications
- Genetics, Bioinformatics, and Biomedical Research
- Renal cell carcinoma treatment
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- Genetic factors in colorectal cancer
- RNA Research and Splicing
- Science, Research, and Medicine
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Ferroptosis and cancer prognosis
- Genetic Mapping and Diversity in Plants and Animals
- Epigenetics and DNA Methylation
- Cardiac Fibrosis and Remodeling
- Medical Imaging and Pathology Studies
- Colorectal Cancer Screening and Detection
- Pancreatic and Hepatic Oncology Research
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Grail (United States)
2024
Menlo School
2017-2024
Guardant (United States)
2018-2020
Stanford University
2013-2014
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...
Circulating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I–III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy. In this retrospective study, 260 patients clinical I NSCLC (180 adenocarcinoma, 80 squamous carcinoma) were allocated (2:1) high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA...
Abstract Summary: RNA sequencing has provided unprecedented resolution of alternative splicing and quantitative trait loci (sQTL). However, there are few tools available for visualizing the genotype-dependent effects at a population level. SplicePlot is simple command line utility that produces intuitive visualization sQTLs their effects. takes mapped reads in BAM format genotype data VCF as input outputs publication-quality Sashimi plots, hive plots structure enabling better investigation...
Abstract Background: Translational research and enrollment in clinical trials are limited by the rarity of individual mutations lack sufficient tissue for comprehensive testing. To address these limitations, we developed GuardantOMNI (OMNI), a highly sensitive 500-gene cfDNA sequencing test requiring as little 2 mL plasma designed broad genomic detection somatic single-nucleotide variants (SNVs) small indels 497 genes, copy number amplifications (CNAs) 106 fusions 21 genes. Additionally,...
Abstract Background: A recent large study found that over 2% of advanced cancer patients have unidentified germline alterations incidentally during next-generation sequencing (NGS) for targetable somatic alterations. However, tissue-based NGS cannot definitively distinguish from mutations without comparison to normal tissue. Because variants typically occur in plasma at allele fractions 1-2 orders magnitude lower than germline, liquid biopsy often enables differentiation incidental...
e15549 Background: Liquid biopsy is a candidate for detection of minimal residual disease (MRD) in early colorectal cancer. Detection circulating tumor (ct)DNA stage cancer challenging given the low abundance ctDNA molecules. We developed tissue agnostic MRD Test to optimize sensitivity and specificity by integrating tumor-specific genomic mutation DNA methylation signatures coupled noise-reduction non-tumor background cfDNA signals. Methods: This was following CLIA, Nex-StoCT Working Group,...
Abstract Introduction: Identifying cancer subtypes is necessary for diagnosis, prognosis determination, and treatment selection. Furthermore, as transformation between increasingly recognized a key resistance mechanism to targeted therapies, serial subtype reassessment likely gain adoption. Cancer have traditionally been determined by pathologists based on histology; more recently, molecular subtyping has performed using IHC, RNAseq, or assays that detect genetic alterations. However, these...
Background: Clonal hematopoiesis (CH) is the acquisition of mutations in hematopoietic progenitor cells that can lead to clonal expansion. Recent studies suggest CH-derived confound interpretation cell-free DNA (cfDNA) sequencing results. To better understand contribution CH cfDNA analysis metastatic cancer setting, we characterized CH-associated alterations observed late-stage patients.Methods: We analyzed somatic variants from profiles over 62,000 patients four cohorts: lung (>35,000),...
Abstract Background: Tumor mutational burden (TMB) has emerged as a predictive biomarker of response to immune checkpoint inhibitor (ICI) therapy. Current panel-based TMB algorithms aggregate signal from certain types somatic variants (e.g. non-synonymous coding SNVs); however, delineating the contributions these and other mutations may refine calculation gene panels. Moreover, early studies suggest possible genomic correlates patient outcome ICI which be complementary TMB. Here, we explore...
Abstract Background: Clonal hematopoiesis (CH) is the acquisition of mutations in hematopoietic progenitor cells that can lead to clonal expansion. Recent studies suggest CH-derived confound interpretation cell-free DNA (cfDNA) sequencing results. To better understand contribution CH cfDNA analysis metastatic cancer setting, we characterized CH-associated alterations observed late-stage patients. Methods: We analyzed somatic variants from profiles over 62,000 patients four cohorts: lung...
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<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...
Abstract Background: Frequencies of germline mutations in BRCA1 and BRCA2 (BRCA1/2) are well-described; however, existing data incomplete regarding the cancer specific spectrum somatic BRCA1/2 (sBRCA) co-occurrence microsatellite instability (MSI), particularly when detected circulating tumor DNA (ctDNA). To better elucidate potential target populations for PARP inhibitor (PARPi) monotherapy combination PARPi-immunotherapy trials provide on frequency sBRCA ctDNA, we conducted a...
Background: Tumor mutational burden (TMB) has emerged as a predictive biomarker of response to immune checkpoint inhibitor (ICI) therapy. Current panel-based TMB algorithms aggregate signal from certain types somatic variants (e.g. non-synonymous coding SNVs); however, delineating the contributions these and other mutations may refine calculation gene panels. Moreover, early studies suggest possible genomic correlates patient outcome ICI which be complementary TMB. Here, we explore landscape...