Detection of structural variants in circulating cell-free DNA from sarcoma patients using next generation sequencing

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Lauren Mc Connell - , Queen's University Belfast (Autor:in)
  • Jana Gazdova - , Queen's University Belfast (Autor:in)
  • Katja Beck - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Shambhavi Srivastava - , Queen's University Belfast (Autor:in)
  • Louise Harewood - , Queen's University Belfast (Autor:in)
  • J. P. Stewart - , Queen's University Belfast (Autor:in)
  • Daniel Hübschmann - , Deutsches Krebsforschungszentrum (DKFZ), Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) (Autor:in)
  • Albrecht Stenzinger - , Deutsches Krebsforschungszentrum (DKFZ), Universität Heidelberg (Autor:in)
  • Hanno Glimm - , Nationales Centrum für Tumorerkrankungen Dresden, Deutsches Konsortium für Translationale Krebsforschung (DKTK) - Dresden, Translational Functional Cancer Genomics Group, Deutsches Krebsforschungszentrum (DKFZ), Nationales Zentrum für Tumorerkrankungen (NCT) Dresden (Autor:in)
  • Christoph E. Heilig - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Stefan Fröhling - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • David Gonzalez - , Queen's University Belfast, Belfast Health and Social Care Trust (Autor:in)

Abstract

Circulating tumour DNA (ctDNA) analysis using next generation sequencing (NGS) is being implemented in clinical practice for treatment stratification and disease monitoring. However, using ctDNA to detect structural variants, a common occurrence in sarcoma, can be challenging. Here, we use a sarcoma-specific targeted NGS panel to identify translocations and copy number variants in a cohort of 12 tissue specimens and matched circulating cell-free DNA (cfDNA) from soft tissue sarcoma patients, including alveolar rhabdomyosarcoma (n = 2), Ewing’s Sarcoma (n = 2), synovial sarcoma (n = 2), extraskeletal myxoid chondrosarcoma (n = 1), clear cell sarcoma (n = 1), undifferentiated round cell sarcoma (n = 1), myxoid liposarcoma (n = 1), alveolar soft part cell sarcoma (n = 1) and dedifferentiated liposarcoma (n = 1). Structural variants were detected in 11/12 (91.6%) and 6/12 (50%) of tissue and plasma samples, respectively. Structural variants were detected in cfDNA at variant allele frequencies >0.2% with an average sequencing depth of 1026×. The results from this cohort show clinical potential for using NGS in ctDNA to aid in the diagnosis and clinical monitoring of sarcomas and warrant additional studies in larger cohorts.

Details

OriginalspracheEnglisch
Aufsatznummer3627
Seiten (von - bis)1-9
Seitenumfang9
FachzeitschriftCancers
Jahrgang12
Ausgabenummer12
PublikationsstatusVeröffentlicht - Dez. 2020
Peer-Review-StatusJa

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • Cell-free DNA, Next generation sequencing, Sarcoma, Translocations