The Need for a Consensus Next-generation Sequencing Panel for Mature Lymphoid Malignancies.
Ontology highlight
ABSTRACT:
SUBMITTER: Sujobert P
PROVIDER: S-EPMC6745936 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Publications
The Need for a Consensus Next-generation Sequencing Panel for Mature Lymphoid Malignancies.
Sujobert Pierre P Le Bris Yannick Y de Leval Laurence L Gros Audrey A Merlio Jean Philippe JP Pastoret Cedric C Huet Sarah S Sarkozy Clémentine C Davi Frédéric F Callanan Mary M Thieblemont Catherine C Sibon David D Asnafi Vahid V Preudhomme Claude C Gaulard Philippe P Jardin Fabrice F Salles Gilles G Macintyre Elizabeth E
HemaSphere 20181227 1
Supplemental Digital Content is available in the text. ...[more]
Similar Datasets
Project description:Next generation sequencing (NGS) identifies alterations that may be potentially targetable by Food and Drug Administration (FDA) approved drugs and/or by available experimental agents that may not have otherwise been contemplated. Many targeted drugs have been developed for diverse solid cancers; a smaller number of genomically targeted drugs have been approved for lymphoid malignancies. We analyzed NGS results from 60 patients with various lymphoid malignancies and found a total of 224 alterations (median per patient = 3). Forty-nine patients (82%) had potentially actionable alterations using FDA-approved drugs and/or experimental therapies; only 11 patients (18%) had no theoretically actionable alterations. Only three patients (5%) had an alteration for which an approved drug in the disease is available (on-label); 45 patients (75%) had an alteration for which an approved drug is available in another disease (off-label). The median number of alterations per patient potentially actionable by an FDA-approved drug was 1. Interestingly, 19 of 60 patients (32%) had intermediate to high tumor mutational burden, which may predict response to certain immunotherapy agents. In conclusion, NGS identifies alterations that may be pharmacologically tractable in most patients with lymphoid malignancies, albeit with drugs that have usually been developed in the context of solid tumors. These observations merit expanded exploration in the clinical trials setting.
| S-EPMC5495179 | biostudies-literature
Project description:Next-generation sequencing has led to a revolution in the study of hematological malignancies with a substantial number of publications and discoveries in the last few years. Significant discoveries associated with disease diagnosis, risk stratification, clonal evolution and therapeutic intervention have been generated by this powerful technology. As part of the post-genomic era, sequencing analysis will likely become part of routine clinical testing and the challenge will ultimately be successfully transitioning from gene discovery to preventive and therapeutic intervention as part of individualized medicine strategies. In this report, we review recent advances in the understanding of hematological malignancies derived through genome-wide sequence analysis.
| S-EPMC3730204 | biostudies-other
Project description:BackgroundNext-generation sequencing (NGS) is a high-throughput technology that has become widely integrated in molecular diagnostics laboratories. Among the large diversity of NGS-based panels, the Trusight Tumor 26 (TsT26) enables the detection of low-frequency variants across 26 genes using the MiSeq platform.MethodsWe describe the inter-laboratory validation and subsequent clinical application of the panel in 399 patients presenting a range of tumor types, including gastrointestinal (GI, 29%), hematologic (18%), lung (13%), gynecological and breast (8% each), among others.ResultsThe panel is highly accurate with a test sensitivity of 92%, and demonstrated high specificity and positive predictive values (95% and 96%, respectively). Sequencing testing was successful in two-thirds of patients, while the remaining third failed due to unsuccessful quality-control filtering. Most detected variants were observed in the TP53 (28%), KRAS (16%), APC (10%) and PIK3CA (8%) genes. Overall, 372 variants were identified, primarily distributed as missense (81%), stop gain (9%) and frameshift (7%) altered sequences and mostly reported as pathogenic (78%) and variants of uncertain significance (19%). Only 14% of patients received targeted treatment based on the variant determined by the panel. The variants most frequently observed in GI and lung tumors were: KRAS c.35G > A (p.G12D), c.35G > T (p.G12V) and c.34G > T (p.G12C).ConclusionsPrior panel validation allowed its use in the laboratory daily practice by providing several relevant and potentially targetable variants across multiple tumors. However, this study is limited by high sample inadequacy rate, raising doubts as to continuity in the clinical setting.
| S-EPMC7546223 | biostudies-literature
Project description:Gliomas account for the majority of primary brain tumors. Glioblastoma is the most common and malignant type. Based on their extreme molecular heterogeneity, molecular markers can be used to classify gliomas and stratify patients into diagnostic, prognostic, and therapeutic clusters. In this work, we developed and validated a targeted next-generation sequencing (NGS) approach to analyze variants or chromosomal aberrations correlated with tumorigenesis and response to treatment in gliomas. Our targeted NGS analysis covered 13 glioma-related genes (ACVR1, ATRX, BRAF, CDKN2A, EGFR, H3F3A, HIST1H3B, HIST1H3C, IDH1, IDH2, P53, PDGFRA, PTEN), a 125 bp region of the TERT promoter, and 54 single nucleotide polymorphisms (SNPs) along chromosomes 1 and 19 for reliable assessment of their copy number alterations (CNAs). Our targeted NGS approach provided a portrait of gliomas' molecular heterogeneity with high accuracy, specificity, and sensitivity in a single workflow, enabling the detection of variants associated with unfavorable outcomes, disease progression, and drug resistance. These preliminary results support its use in routine diagnostic neuropathology.
| S-EPMC9320073 | biostudies-literature
Project description:NGPS is a method for de-novo, full-length protein sequencing in high throughput. The method is based on cleavage of the protein at semi-random sites by microwave-assisted acid hydrolysis (MAAH), enrichment of LC-MS/MS amenable peptides from the hydrolysate by solid-phase-extraction, LC-MS/MS analysis, de-novo long peptide tag sequencing of resulting peptides and assembly of peptide tags into consensus contigs.
2017-04-03 | PXD003804 | Pride
Project description:The chronic behavior of mature lymphoid malignancies, with relapses occurring years apart in many patients, has until recently been unexplained. Patterns of relapse also differ vastly between disease entities, with some being highly curable by chemotherapy whereas others are destined to reemerge after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source of mature lymphoid malignancy and discuss the perspectives.
| S-EPMC5729619 | biostudies-literature
Project description:A critical step in detecting variants from next-generation sequencing data is post hoc filtering of putative variants called or predicted by computational tools. Here, we highlight four critical parameters that could enhance the accuracy of called single nucleotide variants and insertions/deletions: quality and deepness, refinement and improvement of initial mapping, allele/strand balance, and examination of spurious genes. Use of these sequence features appropriately in variant filtering could greatly improve validation rates, thereby saving time and costs in next-generation sequencing projects.
| S-EPMC3371040 | biostudies-literature
Project description:Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.
| S-EPMC5445206 | biostudies-literature
Project description:Background:Genomic profiling is increasingly incorporated into oncology research and the clinical care of cancer patients. We sought to determine physician perception and use of enterprise-scale clinical sequencing at our center, including whether testing changed management and the reasoning behind this decision-making. Patients and methods:All physicians who consented patients to MSK-IMPACT, a next-generation hybridization capture assay, in tumor types where molecular profiling is not routinely performed were asked to complete a questionnaire for each patient. Physician determination of genomic 'actionability' was compared to an expertly curated knowledgebase of somatic variants. Reported management decisions were compared to chart review. Results:Responses were received from 146 physicians pertaining to 1932 patients diagnosed with 1 of 49 cancer types. Physicians indicated that sequencing altered management in 21% (331/1593) of patients in need of a treatment change. Among those in whom treatment was not altered, physicians indicated the presence of an actionable alteration in 55% (805/1474), however, only 45% (362/805) of these cases had a genomic variant annotated as actionable by expert curators. Further evaluation of these patients revealed that 66% (291/443) had a variant in a gene associated with biologic but not clinical evidence of actionability or a variant of unknown significance in a gene with at least one known actionable alteration. Of the cases annotated as actionable by experts, physicians identified an actionable alteration in 81% (362/445). In total, 13% (245/1932) of patients were enrolled to a genomically matched trial. Conclusion:Although physician and expert assessment differed, clinicians demonstrate substantial awareness of the genes associated with potential actionability and report using this knowledge to inform management in one in five patients. Clinical Trial number:NCT01775072.
| S-EPMC5834089 | biostudies-literature
Project description:The symptomatology of lupus nephritis (LN) consists of foamy urine and lower leg edema, as well as such systemic manifestations as oral ulcers, arthralgia/arthritis, and lymphadenopathy. However, these symptoms may appear mild and non-specific. If these symptoms are unrecognized, thus delaying treatment, approximately 10% of LN patients will develop permanent kidney damage and end-stage kidney disease. Therefore, the purpose of this study is to identify a surrogate biomarker for the early detection of LN. In this study, we first adopted next generation sequencing (NGS) in order to screen differential expression levels of microRNA between SLE patients with and without LN. The results of both the NGS and the literature review confirmed the potential of 15 microRNAs through real-time qPCR. We further considered clinical laboratory data for additional analysis. In total, 41 microRNAs demonstrated significant differences through NGS screening. We then verified eight microRNAs from NGS and seven microRNAs from the literature review using the real-time qPCR method in peripheral mononuclear cells. Ultimately, mir-125a-5p, miR-146a-5p, and mir-221-3p were found to be statistically significant not only in the screening study but also in the real-time qPCR verification studies. miR-146a-5p was observed to have a significant correlation with clinical biochemistry markers, as well as to be a surrogate biomarker for the early detection of lupus nephritis. This study is the first to show that the intracellular biomarker miR-146a-5p may serve as a useful specific biomarker for the detection of lupus nephritis among lupus patients in the future, regardless of serum albumin levels and spot urine protein/creatinine ratio.
| S-EPMC6021342 | biostudies-literature