scholarly journals Mixed phenotype acute leukemia contains heterogeneous genetic mutations by next-generation sequencing

Oncotarget ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 8441-8449 ◽  
Author(s):  
Andrés E. Quesada ◽  
Zhihong Hu ◽  
Mark J. Routbort ◽  
Keyur P. Patel ◽  
Rajyalakshmi Luthra ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Acute Leukemia ◽  
Genetic Mutations ◽  
Next Generation ◽  
Mixed Phenotype Acute Leukemia ◽  
Mixed Phenotype ◽  
Generation Sequencing

scholarly journals Power and Promise of Next-Generation Sequencing in Liquid Biopsies and Cancer Control

2020 ◽  
Vol 27 (3) ◽  
pp. 107327482093480
Author(s):  
Ting-Miao Wu ◽  
Ji-Bin Liu ◽  
Yu Liu ◽  
Yi Shi ◽  
Wen Li ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Treatment Plan ◽  
Genetic Mutations ◽  
Specific Gene ◽  
Specific Situation ◽  
Next Generation ◽  
Early Screening ◽  
Liquid Biopsies ◽  
Cancer Management ◽  
Generation Sequencing

Traditional methods of cancer treatment are usually based on the morphological and histological diagnosis of tumors, and they are not optimized according to the specific situation. Precision medicine adjusts the existing treatment regimen based on the patient’s genomic information to make it most suitable for patients. Detection of genetic mutations in tumors is the basis of precise cancer medicine. Through the analysis of genetic mutations in patients with cancer, we can tailor the treatment plan for each patient with cancer to maximize the curative effect, minimize damage to healthy tissues, and optimize resources. In recent years, next-generation sequencing technology has developed rapidly and has become the core technology of precise targeted therapy and immunotherapy for cancer. From early cancer screening to treatment guidance for patients with advanced cancer, liquid biopsy is increasingly used in cancer management. This is as a result of the development of better noninvasive, repeatable, sensitive, and accurate tools used in early screening, diagnosis, evaluation, and monitoring of patients. Cell-free DNA, which is a new noninvasive molecular pathological detection method, often carries tumor-specific gene changes. It plays an important role in optimizing treatment and evaluating the efficacy of different treatment options in clinical trials, and it has broad clinical applications.

scholarly journals Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

2020 ◽  
Vol 38 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Borahm Kim ◽  
Esl Kim ◽  
Seung‐Tae Lee ◽  
June‐Won Cheong ◽  
Chuhl Joo Lyu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Acute Leukemia ◽  
Gene Fusions ◽  
Next Generation ◽  
Novel Gene ◽  
Generation Sequencing

scholarly journals Utility of Combined DNA and RNA Next Generation Sequencing in Leukemias for Identification of Prognostic and Therapeutically Relevant Genomic Alterations in Clinical Practice

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1039-1039
Author(s):  
Catherine C. Coombs ◽  
Aaron D. Viny ◽  
Jie He ◽  
Rachel Kobos ◽  
Doron Lipson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Acute Leukemia ◽  
Consecutive Series ◽  
Genomic Profiling ◽  
Next Generation ◽  
Genomic Alterations ◽  
Dna And Rna ◽  
Generation Sequencing

Abstract Genome and exome sequencing have provided important insights into the biology of hematologic malignancies, and have led to the identification of prognostically relevant mutations and therapeutically targetable genomic alterations. However, the utility of genomic profiling in routine clinical practice remains an area of active investigation, and there is a need for evidence-based approaches to application of these data. Although most adults with acute leukemia relapse after initial therapy, only 25% of acute leukemia patients are enrolled onto clinical trials. Reasons for limited enrollment are multifold, but include a limited understanding by clinicians of genomic alterations, and lack of access to broad-based analytically validated clinical genomic profiling, both hampering the ability of clinicians to enroll patients on genotype-specific, mechanism-based clinical trials. As such, the development of high throughput, state-of-the-art genomic profiling assays for clinical practice, such as FoundationOneHeme, provide an unprecedented opportunity. Here we analyzed a consecutive series of 62 leukemia patients at Memorial Sloan Kettering Cancer Center for whom FoundationOneHeme was performed to determine the incidence and applicability of genomic findings on clinical care. The clinical sample cohort included 17 patients with myelodysplastic syndromes (MDS), 14 patients with acute myeloid leukemia (AML), 14 patients with acute lymphoblastic leukemia (ALL), 6 patients with myeloproliferative neoplasms (MPN), 5 patients with chronic lymphocytic leukemia (CLL), 4 patients with aplastic anemia (AA), and 2 patients with chronic myeloid leukemias (CML). DNA and RNA were successfully extracted from 58/62 samples (94%). Adaptor ligated sequencing libraries were captured by solution hybridization using a custom bait-set targeting 405 cancer-related genes and 31 frequently rearranged genes by DNA-seq, and 265 frequently-rearranged genes by RNA-seq. Samples were sequenced to high depth (Illumina HiSeq) in a CLIA-certified CAP-accredited laboratory (Foundation Medicine), averaging 590x for DNA and >20M total pairs for RNA, to enable the sensitive and specific detection of short variants (substitutions and indels), CNAs and gene fusions. A genomic alteration was characterized as “therapeutic” if it has been shown to determine response or resistance to an available therapy, or mechanism-based trial and “prognostic” if it has been shown to be predictive of outcome by individual disease states. Of the 58 patients with informative genomic data, 84% had at least one pathogenic variant identified. A total of 154 such alterations were identified (2.7 alterations per sample), including 81 base substitutions, 39 indels, 6 splice mutations, 10 CNAs and 18 fusions/rearrangements. 69% of patients had variants identified that were classified as clinically significant. 53% of patients had potential therapeutically relevant genomic alterations, and 43% of patients had prognostically relevant alterations identified. 36% of patients had both therapeutic and prognostic alterations identified. The most common alterations identified in our cohort were TP53 (n= 8), NRAS (n= 6), KMT2A, KRAS, RUNX1 (n= 5), CDKN2A, CDKN2B, SF3B1, TET2 (n= 4). In sum, 54 prognostic and 47 therapeutic genomic alterations were identified. 7 MDS cases, 4 AA cases, 2 AML cases, 2 ALL cases, 1 CML case, and 1 CLL case did not have a pathogenic or actionable allele, demonstrating that almost all patients in our cohort had mutations with biologic and clinical relevance. We also noted a set of variants of unknown significance, including 37 deletions and 26 insertions, which are under investigation in regard to prognostic and therapeutic significance. However, given that at least one genomic variant was identified in the majority of patients, our data demonstrate the utility of this approach in the identification of somatic genomic alterations for prognostic and therapeutic value, and to identify clonal markers which can be used to track molecular response during anti-leukemic therapy. In summary, we analyzed the mutational profiles of leukemia patients using an analytic and clinically validated assay, which allowed us to identify both prognostic and therapeutically relevant mutations in the majority of patients, confirming the utility of comprehensive next-generation sequencing in clinical practice. Disclosures He: Foundation Medicine: Employment. Lipson:Foundation Medicine, Inc.: Employment. Otto:Foundation Medicine, Inc.: Employment. Miller:Foundation Medicine, Inc: Employment. van den Brink:Foundation Medicine, Inc.: Consultancy. Armstrong:Foundation Medicine, Inc.: Consultancy. Stephens:Foundation Medicine: Employment, Equity Ownership. Levine:Foundation Medicine, Inc.: Consultancy.

Genomic analysis for potential targetable mutations in relapsed and refractory germ cell tumors.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 407-407
Author(s):  
Sean Q. Kern ◽  
Lawrence H. Einhorn ◽  
Nabil Adra
Keyword(s):  
Next Generation Sequencing ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Genetic Mutations ◽  
High Dose ◽  
Cell Transplant ◽  
Next Generation ◽  
Genomic Alterations ◽  
Platinum Based Chemotherapy ◽  
Generation Sequencing

407 Background: A large number of metastatic germ cell tumors (GCTs) are cured with platinum-based chemotherapy. Patients that have relapsed or refractory disease can be cured with salvage therapy including salvage surgery, standard dose or high-dose chemotherapy with stem-cell transplant. However, 15-20% of patients with metastatic GCT are incurable with current therapeutic options. We sought to perform a genetic analysis on a cohort of these incurable patients to determine the presence of therapeutically targetable genetic mutations. Methods: After obtaining IRB approval, patients treated at Indiana University for refractory or relapsed GCT from 2016-2019 were analyzed with a next-generation sequencing (NGS) platform. Clinically relevant genomic alterations were reviewed to determine the potential for targeted therapies. Results: 10 patients with testicular (9) or ovarian (1) GCT underwent an analysis of tissue (7), blood (1), or both (2) with a mean 2.9 potential targetable mutations per patient. Four patients had NGS from preserved gonadal tissue removed prior to chemotherapy while 6/10 sample specimens were obtained post standard (1) or high-dose (5) chemotherapy. Potential known therapeutic targets were found in 80% (8/10). Of the platforms that tested biomarkers, high microsatellite instability (MSI) (1/5), intermediate tumor mutational burden (1/4), and high PD-L1 expression of 90% (1/3) was appreciated. The MSI-high patient did not respond to pembrolizumab. A patient with a KIT only mutation did not achieve a response to imatinib. One patient with KRAS, KIT, RAF1, CCND2, MET, AR, CDK6, PDGFRA, EGFR, and BRAF mutations was treated with brentuximab and was progression free for 2.5 months. Common mutations were CCND2 (4/10), RAF1 (2/10), KIT (2/10), and KRAS (2/10). Other mutations actionable in non-GCT tumors included ERCC1, TUBB3, RRMI, PIK3CA, TOPO1 and TP53. Conclusions: NGS identifies potential clinically relevant genomic alterations. Genetic mutations may enable future effective therapies as our understanding of platinum-resistant disease evolves. To our knowledge, this is among the first reports utilizing next-generation sequencing in GCT to direct potential therapeutic agents.

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