The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Feasibility to use whole-genome sequencing as a sole diagnostic method to detect genomic aberrations in pediatric B-cell acute lymphoblastic leukemia


  • Fatemah Rezayee
  • Jesper Eisfeldt
  • Aron Skaftason
  • Ingegerd Öfverholm
  • Shumaila Sayyab
  • Ann Christine Syvänen
  • Khurram Maqbool
  • Henrik Lilljebjörn
  • Bertil Johansson
  • Linda Olsson-Arvidsson
  • Christina Orsmark Pietras
  • Anna Staffas
  • Lars Palmqvist
  • Thoas Fioretos
  • Lucia Cavelier
  • Linda Fogelstrand
  • Jessica Nordlund
  • Valtteri Wirta
  • Richard Rosenquist
  • Gisela Barbany

Summary, in English

Introduction: The suitability of whole-genome sequencing (WGS) as the sole method to detect clinically relevant genomic aberrations in B-cell acute lymphoblastic leukemia (ALL) was investigated with the aim of replacing current diagnostic methods. Methods: For this purpose, we assessed the analytical performance of 150 bp paired-end WGS (90x leukemia/30x germline). A set of 88 retrospective B-cell ALL samples were selected to represent established ALL subgroups as well as ALL lacking stratifying markers by standard-of-care (SoC), so-called B-other ALL. Results: Both the analysis of paired leukemia/germline (L/N)(n=64) as well as leukemia-only (L-only)(n=88) detected all types of aberrations mandatory in the current ALLTogether trial protocol, i.e., aneuploidies, structural variants, and focal copy-number aberrations. Moreover, comparison to SoC revealed 100% concordance and that all patients had been assigned to the correct genetic subgroup using both approaches. Notably, WGS could allocate 35 out of 39 B-other ALL samples to one of the emerging genetic subgroups considered in the most recent classifications of ALL. We further investigated the impact of high (90x; n=58) vs low (30x; n=30) coverage on the diagnostic yield and observed an equally perfect concordance with SoC; low coverage detected all relevant lesions. Discussion: The filtration of the WGS findings with a short list of genes recurrently rearranged in ALL was instrumental to extract the clinically relevant information efficiently. Nonetheless, the detection of DUX4 rearrangements required an additional customized analysis, due to multiple copies of this gene embedded in the highly repetitive D4Z4 region. We conclude that the diagnostic performance of WGS as the standalone method was remarkable and allowed detection of all clinically relevant genomic events in the diagnostic setting of B-cell ALL.


  • Division of Clinical Genetics
  • Translational Genomic and Functional Studies of Leukemia
  • LUCC: Lund University Cancer Centre
  • Genetic and epigenetic studies of pediatric leukemia
  • LTH Profile Area: Engineering Health

Publishing year





Frontiers in Oncology



Document type

Journal article


Frontiers Media S. A.


  • Cancer and Oncology


  • B-cell acute lymphoblastic leukemia
  • class-defining genetic lesions
  • diagnostic validation
  • genomic aberrations
  • whole-genome sequencing



Research group

  • Translational Genomic and Functional Studies of Leukemia
  • Genetic and epigenetic studies of pediatric leukemia


  • ISSN: 2234-943X