Precision Diagnostics in Myeloid Malignancies: Development and Validation of a National Capture‐Based Gene Panel
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 va...
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Published in | Genes chromosomes & cancer Vol. 63; no. 7; pp. e23257 - n/a |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.07.2024
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | The Clinical Genomics platform is supported by national grants from SciLifeLab and the medical faculties at Gothenburg University, Linköping University, Lund University, Karolinska Institutet, Umeå University, Uppsala University, and Örebro University. GMS is supported by the strategic innovation programme Swelife and Vinnova, the Swedish Innovation Agency, the Ministry of Health and Social Affairs, SciLifeLab, the Swedish Childhood Cancer Fund, funding from the participating healthcare regions Region Skåne, Västra Götalandsregionen, Region Östergötland, Region Stockholm, Region Uppsala, Region Västerbotten, Region Örebro län and the medical faculties at Gothenburg University, Linköping University, Lund University, Karolinska Institutet, Umeå University, Uppsala University, and Örebro University. Funding Valtteri Wirta, Richard Rosenquist, Lucia Cavelier, and Thoas Fioretos share senior authorship. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
ISSN: | 1045-2257 1098-2264 1098-2264 |
DOI: | 10.1002/gcc.23257 |