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: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

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

Precision Diagnostics in Myeloid Malignancies : Development and Validation of a National Capture-Based Gene Panel

Author

  • Christina Orsmark-Pietras
  • Anna Lyander
  • Claes Ladenvall
  • Björn Hallström
  • Anna Staffas
  • Hero Awier
  • Aleksandra Krstic
  • Panagiotis Baliakas
  • Gisela Barbany
  • Cecilia Brunhoff Håkansson
  • Anna Gellerbring
  • Anna Hagström
  • Eva Hellström-Lindberg
  • Gunnar Juliusson
  • Vladimir Lazarevic
  • Arielle Munters
  • Tatjana Pandzic
  • Mia Wadelius
  • Joel Ås
  • Linda Fogelstrand
  • Valtteri Wirta
  • Richard Rosenquist
  • Lucia Cavelier
  • Thoas Fioretos
Show all

Summary, in English

Gene panel sequencing has become a common diagnostic tool for detecting somatically acquired mutations in myeloid neoplasms. However, many panels have restricted content, provide insufficient sensitivity levels, or lack clinically validated workflows. We here describe the development and validation of the Genomic Medicine Sweden myeloid gene panel (GMS-MGP), a capture-based 191 gene panel including mandatory genes in contemporary guidelines as well as emerging candidates. The GMS-MGP displayed uniform coverage across all targets, including recognized difficult GC-rich areas. The validation of 117 previously described somatic variants showed a 100% concordance with a limit-of-detection of a 0.5% variant allele frequency (VAF), achieved by utilizing error correction and filtering against a panel-of-normals. A national interlaboratory comparison investigating 56 somatic variants demonstrated highly concordant results in both detection rate and reported VAFs. In addition, prospective analysis of 323 patients analyzed with the GMS-MGP as part of standard-of-care identified clinically significant genes as well as recurrent mutations in less well-studied genes. In conclusion, the GMS-MGP workflow supports sensitive detection of all clinically relevant genes, facilitates novel findings, and is, based on the capture-based design, easy to update once new guidelines become available. The GMS-MGP provides an important step toward nationally harmonized precision diagnostics of myeloid malignancies.

Department/s

  • Translational Genomic and Functional Studies of Leukemia
  • The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy
  • LTH Profile Area: Engineering Health

Publishing year

2024-07

Language

English

Publication/Series

Genes Chromosomes and Cancer

Volume

63

Issue

7

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Medical Genetics
  • Cancer and Oncology

Keywords

  • capture-based gene panel
  • interlaboratory comparison
  • myeloid malignancies
  • paired tumor-normal analysis
  • precision diagnostics
  • somatic variant detection

Status

Published

Research group

  • Translational Genomic and Functional Studies of Leukemia
  • The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy

ISBN/ISSN/Other

  • ISSN: 1045-2257