Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing - NGS targeted capture control cohort

In routine diagnostic pathology, cancer biopsies are preserved by Formalin-Fixed, Paraffin-Embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis and treatment. Here, we present FFPE-Targeted Locus Capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically-relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and novel rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001007711	Control cohort of lymphoma samples sequenced with a hybrid capture panel designed to be able to detect translocations and mutations in lymphoma samples. used in the paper "Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing"	Illumina HiSeq 2500 Illumina HiSeq 4000	19

Publications	Citations
Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing. Allahyar A, Pieterse M, Swennenhuis J, Los-de Vries GT, Yilmaz M, Leguit R, Meijers RWJ, van der Geize R, Vermaat J, Cleven A, van Wezel T, Diepstra A, van Kempen LC, Hijmering NJ, Stathi P, Sharma M, Melquiond ASJ, de Vree PJP, Verstegen MJAM, Krijger PHL, Hajo K, Simonis M, Rakszewska A, van Min M, de Jong D, Ylstra B, Feitsma H, Splinter E, de Laat W. Nat Commun 12: 2021 3361	12

Publications

Citations

Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing.
Allahyar A, Pieterse M, Swennenhuis J, Los-de Vries GT, Yilmaz M, Leguit R, Meijers RWJ, van der Geize R, Vermaat J, Cleven A, van Wezel T, Diepstra A, van Kempen LC, Hijmering NJ, Stathi P, Sharma M, Melquiond ASJ, de Vree PJP, Verstegen MJAM, Krijger PHL, Hajo K, Simonis M, Rakszewska A, van Min M, de Jong D, Ylstra B, Feitsma H, Splinter E, de Laat W. Nat Commun 12: 2021 3361