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Lymphoma

Research & Diagnostics

Chromosomal translocations with immunoglobin (IG) loci are the classic drivers of many B-cell lymphomas. Detection of these translocations is important for diagnosis, prognosis and therapy decisions.

 

The current diagnostic standard is FISH, which has limitations in the detection of cryptic fusions and fusion partners, is not suited for multiplexing, and is laborious. The molecular diagnosis of translocations is not addressed well by current NGS methods. RNAseq will not detect IG enhancer fusions, and conventional targeted DNA sequencing methods are less suited to sequence large structural changes.

 

TLA enables targeted sequencing of all gene fusions including identification of the fusion partner.

 

Soon available

TLA multiplex kit for detection of gene fusions in BCL2, BCL6, MYC. This kit can be customized with other genes. Contact us for more information.

 

Monitoring

Testing for minimal residual disease (MRD) is starting to be implemented for lymphoma patients for patient stratification and to determine prognosis, and monitor treatment efficacy. Clinical studies are ongoing to tailor patient treatment based on MRD levels (Dogliotti I & Ferrero S (2017)).

 

TLA uniquely enables detection of gene fusion breakpoint sequences at nucleotide resolution. Since gene fusions in lymphoma are known to be cancer-driving, clonal events, these breakpoint sequences are ideal markers for sensitive and quantitative MRD testing with PCR. Review our application note to learn more on TLA and NGS for genomic gene fusion breakpoint sequence specific MRD testing in lymphoma and leukaemia.

 

Become a testing partner

We are currently further validating this application. Please contact us if you would like to become a testing partner.

  • Application notes
  • Publications
  • Webinars
  • Application notes
  • Robust detection of structural variants and single nucleotide variants in FFPE
    Robust detection of structural variants and single nucleotide variants in FFPE
  • Publications
  • Targeted Locus Amplification (TLA): A Novel Next Generation Sequencing (NGS) Technology to Detect New Molecular Markers and Monitoring Minimal Residual Disease (MRD) in Mantle Cell and Follicular Lymphoma

    Genuardi E et al. (2017)                                                                                                            

    A.O.U. Citta della Salute e della Scienza di Torino, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Cergentis, Clinica Humanitas/Gavazzeni, University of Modena e Reggio Emilia & University of Torino

  • Personalized Medicine in Lymphoma: Tailoring Treatment According to Minimal Residual Disease

    Dogliotti I & Ferrero S (2017)                                                                                                            

    A.O.U. Citta della Salute e della Scienza di Torino & University of Torino

  • Sequencing Structural Variants in Cancer for Precision Therapeutics

    Macintyre G et al. (2016)                                                                                                            

    University of Cambridge & VU University Medical Center

  • Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study

    Meisel C et al. (2017)                                                                                                            

    DKFZ, Medical Genetic Center Munich, National Center for Tumor Diseases (NCT), TU Dresden, University Kiel

  • Activating ESR1 Mutations Differentially Impact the Efficacy of ER Antagonists

    Toy W et al. (2016)                                                                                                                             

    AstraZeneca, Memorial Sloan Kettering Cancer Center, University of Chicago & University of Illinois at Urbana Champaign

  • Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer

    Ter Brugge P et al. (2016)                                                                                                            

    Bellvitge Biomedical Research Institute Barcelona, Curie Institute, ICREA, Institute of Cancer Research London, The Netherlands Cancer Institute, University of Barcelona & University Medical Center Utrecht

  • Guidelines for cytogenetic investigations in tumours

    Hastings RJ et al. (2015)                                                                                                            

    Charles University Prague, CHUV, Great Ormond St Hospital, Gustave Roussy, Hospital del Mar, Institute of Genomic Medicine, Oslo University Hospital, Ospedale di Circolo-Polo Universitario, Our Lady's Children's Hospital, Oxford University Hospitals NHS Trust, Radboud University Medical Center, St James's Hospital, University of Cagliari, University of Groningen, University Hospital Ghent, UZ Leuven, VU University Medical Center

  • Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping

    De Vree PJP et al.  (2014)                                                                                                                             

    Cergentis, Erasmus Medical Center, Ghent University, Hubrecht Institute-KNAW, Leiden University Medical Center, The Netherlands Cancer Institute, Radboud University Medical Center, University of Amsterdam, University of Groningen, University Medical Center Utrecht & VIB

  • Webinars
  • Applications and principles of TLA-based complete gene sequencing and haplotyping

     

  • Whole genome coverage plot of a multiplex enrichment panel to target relevant SVs and SNVs in lymphoma.
  • Detection of gene fusions in lymphomas (together with Wouter de Laat, Roos Leguit, Stefan Willems). An exemplary case shows an 1.3 Mb insertion in the BCL6 promoter which was not picked up by FISH.
  • MRD was monitored in a MCL patient using IGH rearrangement (blue) and BCL1/IGH translocation (green). For both markers, the quantitative ranges were 5x10-5 and the sensitivities were 10-5 and 5x10-5, respectively. The results showed that the BCL1/IGH sequence obtained by TLA was as useful in MRD monitoring as the IGH rearrangement detected using classic sequencing techniques. Moreover, in the FU1 sample the tumour burden quantification by TLA BCL1/IGH was even higher than the IGH results.
  • Whole genome coverage plot of a multiplex enrichment panel to target relevant SVs and SNVs in lymphoma.
  • Detection of gene fusions in lymphomas (together with Wouter de Laat, Roos Leguit, Stefan Willems). An exemplary case shows an 1.3 Mb insertion in the BCL6 promoter which was not picked up by FISH.
  • MRD was monitored in a MCL patient using IGH rearrangement (blue) and BCL1/IGH translocation (green). For both markers, the quantitative ranges were 5x10-5 and the sensitivities were 10-5 and 5x10-5, respectively. The results showed that the BCL1/IGH sequence obtained by TLA was as useful in MRD monitoring as the IGH rearrangement detected using classic sequencing techniques. Moreover, in the FU1 sample the tumour burden quantification by TLA BCL1/IGH was even higher than the IGH results.

TLA enables

  • Detection of all gene fusions
  • Analysis on FFPE  or cells
  • Multiplexing to detect all relevant mutations in a single DNA-based test
  • Gene fusion breakpoint detection for personalised MRD test development
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For Research Use Only.Not for use in diagnostic procedures.