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 unsuited 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.

In a retrospective validation study with >100 samples, which has been published in Nature Communications, we have shown that FFPE-TLC is a robust method to detect translocations in B-cell lymphoma samples of variable quality and size. The procedure shows clear advantages over FISH and targeted NGS.

In comparison to FISH, FFPE-TLC shows:

  • Higher sensitivity and resolution
  • Detection of all fusion partners and complex rearrangements
  • All translocations (and other mutations) analyzed in a single assay with limited sample input


In comparison to standard targeted NGS methods, FFPE-TLC has the clear advantage that the technology is not dependent on the successful pulldown and recognition of fusion reads for the detection of rearrangements. FFPE-TLC shows:

  • No false negative results due to missed fusion reads in difficult to sequence regions
  • No false positive results due to rearrangement mimic fusion reads
  • A simple, automated bioinformatic workflow without manual curation


Service projects

If you are working on a research project for fusion detection in lymphoma and would like to use our FFPE-TLC panel, please contact us.

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The implementation of minimal residual disease (MRD) testing is starting for lymphoma patients for patient stratification, 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 about TLA and NGS for genomic gene fusion breakpoint sequence-specific MRD testing in lymphoma and leukemia.




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.
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For Research Use Only.Not for use in diagnostic procedures.
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