A5002641296- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Immunotherapy and Immune Responses
- Pancreatic and Hepatic Oncology Research
- Lymphoma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Ferroptosis and cancer prognosis
- Lung Cancer Research Studies
- Bladder and Urothelial Cancer Treatments
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Multiple and Secondary Primary Cancers
- vaccines and immunoinformatics approaches
- Ovarian cancer diagnosis and treatment
- Cutaneous Melanoma Detection and Management
- Glioma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Gastric Cancer Management and Outcomes
- BRCA gene mutations in cancer
Foundation Medicine (United States)
2016-2025
Editas Medicine (United States)
2016-2020
Bristol-Myers Squibb (United States)
2010-2018
The University of Texas MD Anderson Cancer Center
2018
Loyola University Chicago
2018
Caris Life Sciences (United States)
2018
University of Chicago
2017-2018
Columbia University Irving Medical Center
2018
Texas Health Dallas
2018
Albany Medical Center Hospital
2018
High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown be more significantly associated with response PD-1 PD-L1 blockade immunotherapy than or expression, as measured by immunohistochemistry (IHC). The distribution TMB the subset patients high not well characterized in majority cancer types. In this study, we compare a targeted comprehensive genomic profiling (CGP) assay exome sequencing simulate expected variance when...
Abstract KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine efficacy PD-1 inhibitors these subgroups. Objective response rates to blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) (P < 0.001) Stand Up To Cancer (SU2C) cohort (174 patients) with LUAC patients treated nivolumab CheckMate-057 phase III...
Therapeutic antibodies blocking programmed death-1 and its ligand (PD-1/PD-L1) induce durable responses in a substantial fraction of melanoma patients. We sought to determine whether the number and/or type mutations identified using next-generation sequencing (NGS) panel available clinic was correlated with response anti-PD-1 melanoma. Using archival samples from anti-PD-1/PD-L1-treated patients, we performed hybrid capture-based NGS on 236-315 genes T-cell receptor (TCR) initial validation...
Background Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase interrogated genomic sequence, demonstrates predictive biomarker potential for identification patients with cancer most likely to respond immune checkpoint inhibitors. TMB is optimally calculated by whole exome sequencing (WES), but next-generation targeted panels provide estimates in a time-effective and cost-effective manner. However, differences panel size gene coverage, addition underlying...
Background: The clinical application of PD1/PD-L1 targeting checkpoint inhibitors in colorectal cancer (CRC) has largely focused on a subset microsatellite instable (MSI-high) patients. However, the proposed genotype that sensitizes these patients to immunotherapy is not captured by MSI status alone. Estimation tumor mutational burden (TMB) from comprehensive genomic profiling validated against whole exome sequencing and linked response metastatic melanoma, urothelial bladder non-small cell...
Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), 2 (PDCD1LG2 PDL2), and Janus kinase (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting high response rates to (PD-1)/programmed (PD-L1) blockade. The prevalence utility of PDL1 amplification as a biomarker PD-1/PD-L1 blockade are unknown other tumors.To examine the its solid tumors.This retrospective study (October 1, 2012, October 2017) used deidentified tumor database from commercial company...
Abstract Background Pediatric brain tumors are the leading cause of death for children with cancer in U.S. Incorporating next-generation sequencing data both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, therapeutic decision-making. Materials Methods We performed comprehensive genomic profiling on 282 (157 pHGGs, 125 pLGGs), 315 cancer-related genes calculating tumor mutational burden (TMB; mutations per megabase [Mb]). Results In pLGGs, we...
Abstract Neoantigen presentation arises as a result of tumor-specific mutations and is critical component immune surveillance that can be abrogated by somatic LOH the human leukocyte antigen class I (HLA-I) locus. To understand role HLA-I in oncogenesis treatment, we utilized pan-cancer genomic dataset 83,644 patient samples, small subset which had treatment outcomes with checkpoint inhibitors (ICI). was common (17%) unexpectedly nonlinear relationship tumor mutational burden (TMB). frequent...
Microsatellite instability (MSI) is an important biomarker for predicting response to immune checkpoint inhibitor therapy, as emphasized by the recent approval MSI-high (MSI-H) solid tumors. Herein, we describe and validate a novel method determining MSI status from next-generation sequencing comprehensive genomic profiling assay using formalin-fixed, paraffin-embedded samples. This 97% (65/67) concordant with current standards, PCR immunohistochemistry. We further apply this >67,000 patient...
BACKGROUND In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations HER2, or its dimerization partner HER3, can underlie sensitivity HER2‐targeted therapies. METHODS this study, 8887 cases were evaluated by comprehensive genomic profiling 315 cancer‐related genes, tumor mutational burden, and microsatellite instability. This...
9017 Background: Immune checkpoint inhibitor (ICPI) therapies, including nivolumab and pembrolizumab, have been FDA-approved in squamous non-squamous non-small cell (LC). Current IHC based diagnostics are challenged by assay slide scoring issues, more robust comprehensive biomarkers of ICPI efficacy needed. Methods: Comprehensive genomic profiling (CGP) was performed on FFPE specimens during the course clinical care. TMB (mutations/Mb) assessed as number somatic, coding, base substitution...
Abstract Neurotrophic tropomyosin receptor kinase ( NTRK) gene fusions are rare oncogenic drivers in solid tumours. This study aimed to interrogate a large real-world database of comprehensive genomic profiling data describe the landscape and prevalence NTRK fusions. fusion-positive tumours were identified from FoundationCORE ® >295,000 cancer patients. We investigated concomitant fusions, predicted patient ancestry compared cohort with entrectinib clinical trial cohorts (ALKA-372-001...
•Estimation of TMB varies across different panels, with panel size, gene content and bioinformatics pipelines contributing to empirical variability.•Panel sizes greater than 667Kb are necessary maintain adequate PPA NPA for calling high versus low the range cutoffs used in practice.•Statistical calibration can achieve more consistent results panels allows comparison values various assays. BackgroundTumor mutational burden (TMB) measurements aid identifying patients who likely benefit from...
Abstract Tumor mutational burden (TMB) in circulating tumor DNA (ctDNA) has shown promise predicting benefit from PD-L1/PD-1 inhibitors retrospective studies. Aiming to assess blood TMB (bTMB) prospectively, we conducted B-F1RST ( NCT02848651 ), an open-label, phase 2 trial that evaluated bTMB as a predictive biomarker for first-line atezolizumab monotherapy locally advanced or metastatic stage IIIB–IVB non-small cell lung cancer n = 152). The co-primary endpoints were investigator-assessed...
Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)-an open-label, global, multicohort trial-evaluated the safety and efficacy of first-line targeted therapies or patients with unresectable Stage IIIB IV advanced metastatic who were selected status using blood-based next-generation sequencing. In Phase 3 cohort C evaluating (b)TMB atezolizumab efficacy, bTMB ≥10 (N = 471) randomized 1:1...
Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape KRAS-altered cancers. We performed a pan-cancer analysis samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive profiling; additional analyses included 62,369 liquid biopsy and 7241 pediatric samples. 23% had alterations; 88% were mutations, most commonly G12D/G12V/G12C/G13D/G12R, prevalence was similar biopsies. Co-alteration landscapes largely across...
One of the great challenges in therapeutic oncology is determining who might achieve survival benefits from a particular therapy. Studies on longitudinal circulating tumor DNA (ctDNA) dynamics for prediction have generally been small or nonrandomized. We assessed ctDNA across 5 time points 466 non-small-cell lung cancer (NSCLC) patients randomized phase 3 IMpower150 study comparing chemotherapy-immune checkpoint inhibitor (chemo-ICI) combinations and used machine learning to jointly model...
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)β superfamily ligands that regulate many crucial aspects embryonic development and organogenesis. Unlike other TGFβ ligands, co-receptors for BMP have not been described. Here we show DRAGON, a glycosylphosphatidylinositol-anchored member repulsive guidance molecule family, which is expressed early in developing nervous system, enhances but signaling. DRAGON binds directly to BMP2 BMP4 BMP7 or ligands. The...
// Celina Ang 1 , Samuel J. Klempner 2 Siraj M. Ali 3 Russell Madison Jeffrey S. Ross Eric A. Severson David Fabrizio Aaron Goodman 4 Razelle Kurzrock James Suh and Sherri Z. Millis Department of Medicine, Division Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA Cedars-Sinai Medical Center, Los Angeles, CA, Foundation Cambridge, MA, Hematology Oncology, Moores University California San Diego, Correspondence to: Ang, email: Celina.ang@mssm.edu Keywords:...
Tumor mutational burden (TMB) is a potential biomarker associated with response to immune checkpoint inhibitor therapies. The prognostic value TMB in the absence of immunotherapy uncertain.To assess prevalence high (TMB-H) and its association overall survival (OS) among patients not treated same 10 tumor types from KEYNOTE-158 study.This retrospective cohort study evaluated TMB-H, assessed by Foundation Medicine (FMI) defined as at least mutations/megabase (mut/Mb) immunotherapy. Data were...
Genomic fusions of the anaplastic lymphoma kinase gene (ALK) are a well-established therapy target in non-small cell lung cancer (NSCLC). From survey 114,200 clinical cases, we determined prevalence ALK rearrangements (rALK) non-NSCLC tumors and report their responsiveness to therapies targeting ALK.Comprehensive genomic profiling relapsed metastatic malignancies, including both solid hematolymphoid cancers, was performed using hybrid-capture, adaptor ligation-based next-generation...