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Precision Diagnostics in Myeloid Malignancies: Development and Validation of a National Capture-Based Gene Panel.
Orsmark-Pietras, Christina; Lyander, Anna; Ladenvall, Claes; Hallström, Björn; Staffas, Anna; Awier, Hero; Krstic, Aleksandra; Baliakas, Panagiotis; Barbany, Gisela; Håkansson, Cecilia Brunhoff; Gellerbring, Anna; Hagström, Anna; Hellström-Lindberg, Eva; Juliusson, Gunnar; Lazarevic, Vladimir; Munters, Arielle; Pandzic, Tatjana; Wadelius, Mia; Ås, Joel; Fogelstrand, Linda; Wirta, Valtteri; Rosenquist, Richard; Cavelier, Lucia; Fioretos, Thoas.
Afiliação
  • Orsmark-Pietras C; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Lyander A; Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden.
  • Ladenvall C; Clinical Genomics Lund, Science for Life Laboratory, Lund University, Lund, Sweden.
  • Hallström B; School of Engineering Sciences in Chemistry, Biotechnology and Health, Clinical Genomics Stockholm, Science Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Staffas A; Department of Microbiology, Tumor and Cell Biology, Clinical Genomics Stockholm, Science Life Laboratory, Karolinska Institutet, Solna, Sweden.
  • Awier H; Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Krstic A; Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden.
  • Baliakas P; Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Barbany G; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Sweden.
  • Håkansson CB; Department of Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
  • Gellerbring A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Hagström A; Department of Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
  • Hellström-Lindberg E; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Juliusson G; Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Lazarevic V; Department of Clinical Genetics, Uppsala University Hospital, Uppsala, Sweden.
  • Munters A; Department of Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
  • Pandzic T; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Wadelius M; Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden.
  • Ås J; Department of Microbiology, Tumor and Cell Biology, Clinical Genomics Stockholm, Science Life Laboratory, Karolinska Institutet, Solna, Sweden.
  • Fogelstrand L; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Wirta V; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Rosenquist R; Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
  • Cavelier L; Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
  • Fioretos T; Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Genes Chromosomes Cancer ; 63(7): e23257, 2024 Jul.
Article em En | MEDLINE | ID: mdl-39031442
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Medicina de Precisão Limite: Humans País/Região como assunto: Europa Idioma: En Revista: Genes Chromosomes Cancer Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Suécia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Medicina de Precisão Limite: Humans País/Região como assunto: Europa Idioma: En Revista: Genes Chromosomes Cancer Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Suécia