A5061220833- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Gastric Cancer Management and Outcomes
- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Renal cell carcinoma treatment
- Pancreatic and Hepatic Oncology Research
- Molecular Biology Techniques and Applications
- Lung Cancer Research Studies
- Bladder and Urothelial Cancer Treatments
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Renal and related cancers
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Melanoma and MAPK Pathways
- Ferroptosis and cancer prognosis
- Genomics and Rare Diseases
- DNA Repair Mechanisms
- Prostate Cancer Treatment and Research
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Esophageal Cancer Research and Treatment
- RNA modifications and cancer
Guardant (United States)
2017-2024
Massachusetts General Hospital
2023
Samsung Medical Center
2019
Sungkyunkwan University
2019
University of Pittsburgh Medical Center
2018
The University of Texas Southwestern Medical Center
2015
Cancer Genetics (United States)
2015
University of Michigan
2015
University of Wisconsin–Madison
2011
St. Jude Children's Research Hospital
2008
Abstract Purpose: To analytically and clinically validate a circulating cell-free tumor DNA sequencing test for comprehensive genotyping demonstrate its clinical feasibility. Experimental Design: Analytic validation was conducted according to established principles guidelines. Blood-to-blood comprised blinded external comparison with droplet digital PCR across 222 consecutive biomarker-positive samples. Blood-to-tissue of calls those documented in the medical record 543 lung cancer patients....
Abstract Mutant-selective KRASG12C inhibitors, such as MRTX849 (adagrasib) and AMG 510 (sotorasib), have demonstrated efficacy in KRASG12C-mutant cancers, including non–small cell lung cancer (NSCLC). However, mechanisms underlying clinical acquired resistance to inhibitors remain undetermined. To begin define the mechanistic spectrum of resistance, we describe a patient with NSCLC who developed polyclonal emergence 10 heterogeneous alterations serial cell-free DNA spanning four genes (KRAS,...
Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order investigate the criteria and processes assigning pathogenicity of specific variants estimate frequency patients European African ancestry, we classified potentially actionable pathogenic single-nucleotide (SNVs) all 4300 European- 2203 African-ancestry participants sequenced by NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected...
Abstract Purpose: Gastroesophageal adenocarcinoma (GEA) has a poor prognosis and few therapeutic options. Utilizing 73-gene plasma-based next-generation sequencing (NGS) cell-free circulating tumor DNA (ctDNA-NGS) test, we sought to evaluate the role of ctDNA-NGS in guiding clinical decision-making GEA. Experimental Design: We evaluated large cohort (n = 2,140 tests; 1,630 patients) results (including 369 clinically annotated patients). Patients were assessed for genomic alteration (GA)...
Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for genomic profiling that overcomes many limitations traditional tissue-based analysis. We examined cfDNA as a tool to inform patients with BTC and generate novel insights into tumor biology.We analyzed next-generation sequencing data 2068 samples from 1671 generated Guardant360. carried out annotation on multi-institutional subset (n =...
Aim: Genomically matched trials in primary brain tumors (PBTs) require recent tumor sequencing. We evaluated whether circulating DNA (ctDNA) could facilitate genomic interrogation these patients. Methods: Data from 419 PBT patients tested clinically with a ctDNA NGS panel at CLIA-certified laboratory were analyzed. Results: A total of 211 (50%) had ≥1 somatic alteration detected. Detection was highest meningioma (59%) and gliobastoma (55%). Single nucleotide variants detected 61 genes,...
To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated immune checkpoint inhibitors. Retrospective analysis metastatic castration-resistant cancer (mCRPC) MSI-H tumor detected by commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September...
BACKGROUND Biomarker‐guided clinical trials are increasingly common in metastatic urothelial carcinoma (mUC), yet patients for whom contemporary tumor tissue is not available eligible. Technological advancements sequencing have made cell‐free circulating DNA (cfDNA) next‐generation (NGS) readily the clinic. The objective of current study was to determine whether genomic profile mUC detected by NGS cfDNA similar historical studies. A secondary frequency alterations (GAs) differed between...
PURPOSE Although the majority of patients with metastatic non–small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in frontline setting, predicting which experience durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS Patients mNSCLC receiving pembrolizumab monotherapy or combination chemotherapy underwent 74-gene next-generation sequencing panel on blood samples obtained at baseline and 9 weeks. The change...
Liquid biopsy (LB) can detect actionable genomic alterations in plasma circulating tumor DNA beyond tissue testing (TT) alone advanced non-small cell lung cancer (NSCLC) patients. We estimated the cost-effectiveness of adding LB to TT Canadian healthcare system.
PARP inhibitors (PARPi) provide an effective maintenance option for patients with BRCA- or PALB2-mutated pancreatic cancer. However, mechanisms of PARPi resistance and optimal post-PARPi therapeutic strategies are poorly characterized.
Chromosomal microarray analysis (CMA) for unexplained anomalies and developmental delay has improved diagnosis rates, but results classified as variants of uncertain significance (VUS) may challenge both clinicians families. We explored the impact such on families, including parental knowledge, understanding interpretation. Semi-structured telephone interviews were conducted with parents (N = 14) who received genetic counseling a VUS in their child. Transcripts analyzed through an iterative...
To effectively articulate the results of exome and genome sequencing we refined structure content molecular test reports. communicate a randomized control trial aimed at evaluation for clinical medicine, developed structured narrative report. With feedback from genetics non‐genetics professionals, separate indication‐specific incidental findings Standard report elements were supplemented with research study‐specific language, which highlighted limitations provided detailed, results,...
MSI-H identified by ctDNA: prevalence across 21 advanced cancers and outcomes from >700 patients.
Somatic alterations in circulating tumor DNA (ctDNA) may be associated with treatment response or prognosis prostate cancer (PCa). The goal was to characterize androgen receptor gene (AR) amplifications and mutations detected ctDNA from patients PCa further understand the somatic genetic heterogeneity of advanced cancer.This study included a heterogeneous group 892 (predominantly castrate-resistant cancer) AR that underwent next-generation sequencing 54 73 genes via Guardant360 testing...
IntroductionMET amplification is a potentially actionable resistance mechanism in ALK-rearranged (ALK+) lung cancer. Studies describing treatment outcomes of this molecular subgroup are lacking.MethodsWe assembled cohort patients with ALK+ cancer and acquired MET (identified by tissue or plasma) who received regimens targeting both ALK MET. Efficacy safety were assessed using the Response Evaluation Criteria Solid Tumors version 1.1 Common Terminology for Adverse Events 4.03,...
Tissue-agnostic indications for targeted therapies have expanded options patients with advanced solid tumors. The Food and Drug Administration approvals of the programmed death-ligand 1 inhibitor pembrolizumab TRK inhibitors larotrectinib entrectinib provide rationale next-generation sequencing (NGS) in effectively all tumor given potential clinical responses even otherwise refractory disease. As proof concept, this case report describes a 64-year-old woman triple-negative breast cancer to...
The role of circulating cell-free tumor DNA (ctDNA) as an adjunct to tissue genomic profiling is poorly defined in metastatic renal cell carcinoma (mRCC). In this study, we aim validate previous findings related alteration (GA) frequency ctDNA and determine the concordance between tissue-based patients with mRCC.Results 839 mRCC who had assessment a Clinical Laboratory Improvement Amendments (CLIA)-certified assay November 2016 December 2019 were collected. Tissue-based was collected when...
While tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in anaplastic lymphoma (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC), clinical outcomes vary and acquired resistance remains a significant challenge. We conducted retrospective study of patients with ALK-positive NSCLC who had clinico-genomic data independently collected from two academic institutions (n = 309). This was paired large-scale genomic cohort underwent liquid biopsies 1,118). Somatic...