TY - JOUR
T1 - Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing
AU - Allahyar, Amin
AU - Pieterse, Mark
AU - Swennenhuis, Joost
AU - Los-de Vries, G. Tjitske
AU - Yilmaz, Mehmet
AU - Leguit, Roos
AU - Meijers, Ruud W. J.
AU - van der Geize, Robert
AU - Vermaat, Joost
AU - Cleven, Arjen
AU - van Wezel, Tom
AU - Diepstra, Arjan
AU - van Kempen, L. on C.
AU - Hijmering, Nathalie J.
AU - Stathi, Phylicia
AU - Sharma, Milan
AU - Melquiond, Adrien S. J.
AU - de Vree, Paula J. P.
AU - Verstegen, Marjon J. A. M.
AU - Krijger, Peter H. L.
AU - Hajo, Karima
AU - Simonis, Marieke
AU - Rakszewska, Agata
AU - van Min, Max
AU - de Jong, Daphne
AU - Ylstra, Bauke
AU - Feitsma, Harma
AU - Splinter, Erik
AU - de Laat, Wouter
N1 - Funding Information: We thank Cheryl Dambrot for the helpful comments on the manuscript. The work conducted by the Hubrecht Institute was supported by KWF/Alpe project 11632/2018-1; TKI project LSHM15017 (SuperGeneSeq); Oncode Institute. The work conducted by Cergentis has received funding from the European Union’s Horizon 2020 SME instruments program SEQURE under grant agreement No. 806446. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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 previously uncharacterized 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.
AB - 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 previously uncharacterized 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.
UR - http://www.scopus.com/inward/record.url?scp=85107561243&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-021-23695-8
DO - https://doi.org/10.1038/s41467-021-23695-8
M3 - Article
C2 - 34099699
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3361
ER -