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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Lauren Mc Connell - , Queen's University Belfast (Author)
  • Jana Gazdova - , Queen's University Belfast (Author)
  • Katja Beck - , German Cancer Research Center (DKFZ) (Author)
  • Shambhavi Srivastava - , Queen's University Belfast (Author)
  • Louise Harewood - , Queen's University Belfast (Author)
  • J. P. Stewart - , Queen's University Belfast (Author)
  • Daniel Hübschmann - , German Cancer Research Center (DKFZ), Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) (Author)
  • Albrecht Stenzinger - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Hanno Glimm - , National Center for Tumor Diseases Dresden, German Cancer Consortium (DKTK) Partner Site Dresden, Translational Functional Cancer Genomics Group, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT) Dresden (Author)
  • Christoph E. Heilig - , German Cancer Research Center (DKFZ) (Author)
  • Stefan Fröhling - , German Cancer Research Center (DKFZ) (Author)
  • David Gonzalez - , Queen's University Belfast, Belfast Health and Social Care Trust (Author)

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

Original languageEnglish
Article number3627
Pages (from-to)1-9
Number of pages9
JournalCancers
Volume12
Issue number12
Publication statusPublished - Dec 2020
Peer-reviewedYes

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

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