scholarly journals Genetic heterogeneity in B-cell lymphoma detected by next-generation sequencing (NGS) technology in a cohort of 150 Chinese patients

2017 ◽  
Vol 35 ◽  
pp. 280-281
Author(s):  
Y. Chen ◽  
J. Lu ◽  
G. Chen
Keyword(s):  
Next Generation Sequencing ◽  
B Cell ◽  
Genetic Heterogeneity ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chinese Patients ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma

Blood ◽  
2013 ◽  
Vol 122 (5) ◽  
pp. 726-733 ◽  
Author(s):  
Hakim Bouamar ◽  
Saman Abbas ◽  
An-Ping Lin ◽  
Long Wang ◽  
Daifeng Jiang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Next Generation ◽  
Key Points ◽  
Sequencing Strategy ◽  
Targeted Capture ◽  
Generation Sequencing ◽  
Capture Sequencing

Key Points Targeted capture/next-generation sequencing is a powerful tool for the diagnosis of known and discovery of new IGH fusions in DLBCL. IGH-mediated deregulation of IRF8 and EBF1 in DLBCL is characterized by induction of AID and BCL6, suppression of PRDM1, and antiapoptosis.

scholarly journals Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

2016 ◽  
Vol 22 (12) ◽  
pp. 2919-2928 ◽  
Author(s):  
Sydney Dubois ◽  
Pierre-Julien Viailly ◽  
Sylvain Mareschal ◽  
Elodie Bohers ◽  
Philippe Bertrand ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Next Generation ◽  
Large B Cell Lymphoma ◽  
Molecular Divergence ◽  
Generation Sequencing ◽  
Large B Cell

scholarly journals Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and Non-L265P Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4097-4097
Author(s):  
Sydney Dubois ◽  
Pierre-Julien Viailly ◽  
Elodie Bohers ◽  
Philippe Bertrand ◽  
Philippe Ruminy ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Next Generation ◽  
Large B Cell Lymphoma ◽  
Pathway Activation ◽  
Generation Sequencing ◽  
Myd88 L265p ◽  
Large B Cell

Abstract Introduction: MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of Activated B-Cell like (ABC) Diffuse Large B Cell Lymphoma (DLBCL), leading to constitutive NFkB pathway activation. The frequency of MYD88 mutations in DLBCL and other hematologic malignancies is well described; however, there has not yet been a large-scale study of a MYD88 mutated patient cohort with additional Next Generation Sequencing (NGS), copy number variation (CNV), and gene expression data, in order to thoroughly characterize the associated genomic profiles of these patients. The aims of our study were to compare the L265P and non-L265P mutations in terms of pathological and genetic features, to better detail the genomic background associated with MYD88 mutations in order to delineate patients potentially sensitive to targeted therapies, and to define the prognostic value of MYD88 mutations according to different genomic contexts. Methods: A cohort of 361 DLBCL patients (94 MYD88 mutant and 267 MYD88 wild-type) was selected among the prospective, multicenter and randomized LNH-03B and LNH09-7B (NCT01195714) LYSA trials, as well as among patients sequenced at our institution as part of routine procedure. Cell of origin (COO) classification was obtained with HGU133+2.0 Affymetrix GeneChip arrays for 214 patients, with RT-MLPA for 77 patients1 and with Hans immunohistochemistry (IHC) method for 49 patients. All cases were submitted to next generation sequencing (NGS) focusing on 34 genes (Lymphopanel2) in order to analyze associated mutations and copy number variations (CNVs), as well as IHC, FISH, and clinical and prognostic analyses. Results: Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis segregated subgroups according to associated genetic alterations among patients with either MYD88 L265P or non-L265P mutations. As such, clustering separated MYD88 L265P mutated DLBCL with associated PIM1 (52%), CD79B (52%), KMT2D (42%), and PRDM1 (32%) mutations, as well as MYD88 L265P mutated DLBCL with CDKN2A/B (67%/50%), PRDM1 (57%) and TNFAIP3 (52%) CNVs. We showed that associated CD79B and MYD88 L265P mutations act synergistically to increase NFkB pathway activation, although the majority of ABC MYD88 L265P mutant cases harbor downstream NFkB alterations, which can potentially predict BTK inhibitor resistance. Of note, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated CD79B mutations significantly improved the survival of MYD88 L265P mutant ABC DLBCL in our cohort both in OS (p=0.02) and PFS (p=0.01), whereas the association of CARD11 or TNFAIP3 alterations did not impact survival. Interestingly, MYD88 mutant DLBCL cases were significantly more likely to experience central nervous system (CNS) relapse than MYD88 WT cases (p=0.02), as were MYD88 L265P mutant cases specifically (p=0.03). This result still tended toward statistical significance when considering only ABC patients (7 of 11 ABC CNS-relapsing cases were MYD88 mutant, p=0.1) but would have to be confirmed in a larger cohort. Conclusions: This study highlights the relative heterogeneity of MYD88 mutant DLBCBL, adding to the field's knowledge of the distinct genetic backgrounds of these subgroups. Our data highlights the theranostic and prognostic relevance of examining MYD88 and associated genomic alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy. 1. Mareschal S, Ruminy P, Bagacean C, et al. Accurate Classification of Germinal Center B-Cell-Like/Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Using a Simple and Rapid Reverse Transcriptase-Multiplex Ligation-Dependent Probe Amplification Assay: A CALYM Study. The Journal of molecular diagnostics : JMD. 2015;17(3):273-283. 2. Dubois S, Viailly P-J, Mareschal S, et al. Next Generation Sequencing in Diffuse Large B Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016;22(12):2919-2928. Disclosures Salles: Novartis: Consultancy, Honoraria; Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding.

scholarly journals Molecular Fingerprinting of Anatomically and Temporally Distinct B-Cell Lymphoma Samples by Next-Generation Sequencing to Establish Clonal Relatedness

2018 ◽  
Vol 143 (1) ◽  
pp. 105-111
Author(s):  
Anna P. Matynia ◽  
K. David Li ◽  
Philippe Szankasi ◽  
Jonathan Schumacher ◽  
Michael Liew ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Translocation Breakpoint ◽  
Derivative Chromosome ◽  
Next Generation ◽  
Molecular Fingerprint ◽  
Clonal Relatedness ◽  
Generation Sequencing

Context.— B-cell lymphomas exhibit balanced translocations that involve immunoglobulin loci and result from aberrant V(D)J recombination, class switch recombination, or somatic hypermutation. Although most of the breakpoints in the immunoglobulin loci occur in defined regions, those in the partner genes vary; therefore, it is unlikely that 2 independent clones would share identical breakpoints in both partners. Establishing whether a new lesion in a patient with history of lymphoma represents recurrence or a new process can be relevant. Polymerase chain reaction (PCR)–based clonality assays used in this setting rely only on evaluating the length of a given rearrangement. In contrast, next-generation sequencing (NGS) provides the exact translocation breakpoint at single-base resolution. Objective.— To determine if translocation breakpoint coordinates can serve as a molecular fingerprint unique to a distinct clonal population. Design.— Thirty-eight follicular lymphoma/diffuse large B-cell lymphoma samples collected from different anatomic sites and/or at different time points from 18 patients were analyzed by NGS. For comparison, PCR-based B-cell clonality and fluorescence in situ hybridization studies were performed on a subset of cases. Results.— IGH-BCL2 rearrangements were detected in all samples. The breakpoint coordinates on derivative chromosome(s) were identical in all samples from a given patient, but distinct between samples derived from different patients. Additionally, 5 patients carried a second rearrangement also with conserved breakpoint coordinates in the follow-up sample(s). Conclusions.— Breakpoint coordinates in the immunoglobulin and partner genes can be used to establish clonal relatedness of anatomically/temporally distinct lesions. Additionally, an NGS-based approach has the potential to detect secondary translocations that may have prognostic and therapeutic significance.

Mutational landscape of AKT1/2/3 in Chinese patients with solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Hui Kong ◽  
Weijia Fang ◽  
Haibo Mou ◽  
Feng Xiao Chen ◽  
Lingxiang Liu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Chinese Patients ◽  
Great Promise ◽  
Central Component ◽  
Next Generation ◽  
Gene Panel Testing ◽  
Different Types ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

e15566 Background: As a central component of PI3K/AKT pathway, AKT serves as an attractive target of anti-cancer strategy with various AKT inhibitors, which show great promise in phase I/II clinical trials. This study aimed to investigate AKT1/2/3 status in different types of cancers by using next generation sequencing (NGS). Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10,010 Chinese patients with solid tumors and subjected to next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations, tumor mutational burden (TMB) values, and microsatellite instability (MSI) status were assessed with a mean coverage of 1000X, including single base substitutions, short and long insertion/deletions, copy number variations, gene fusions, and rearrangements. Genomic data and immune checkpoint inhibitors (ICIs) treatment outcome of a cohort of 1610 patients with solid tumors were derived from cBioPortal (MSKCC, Nat Genet. 2019). Results: AKT1/2/3 were found to be mutually exclusive with each other and accounted for 3.4% in this cohort. The frequencies of AKT1/2/3 variations were 1.1%, 1.6%, and 0.8%, respectively. The most common co-altered genes associated with AKT1/2/3 variations were TP53 (69.4%), PIK3CA (19.3%), KRAS (19%), CCNE1 (18.4%), CDKN2A (16.6%), and 11q13 (6.5%). AKT1/2/3 variations were significantly associated with higher TMB, and independent of MSI status. Outcome data from the MSKCC cohort showed that patients with AKT1/2/3 variations had a remarkable clinical benefit to ICIs treatment compared to patients with wild-type AKT1/2/3 in overall survival (OS) (NA vs 18 months, p = 0.009). Furthermore, AKT1/2/3 variations were independent risk factors of OS (HR: 0.55, 95%CI: 0.34-0.87, p = 0.012). Conclusions: The prevalence of AKT1/2/3 somatic alterations across different types of solid tumors in China was 3.4%. AKT1/2/3 variations were associated with an increased TMB and favorable response to ICIs, suggesting that A KT1/2/3 variations may be biomarkers for guiding anti-AKT agents and ICI treatment.

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