Research Papers: Pathology:

Routine clinical mutation profiling using next generation sequencing and a customized gene panel improves diagnostic precision in myeloid neoplasms

Stephan Bartels, Elisa Schipper, Britta Hasemeier, Hans Kreipe and Ulrich Lehmann _

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Oncotarget. 2016; 7:30084-30093. https://doi.org/10.18632/oncotarget.8310

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Stephan Bartels1, Elisa Schipper1, Britta Hasemeier1, Hans Kreipe1 and Ulrich Lehmann1

1 Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany

Correspondence to:

Ulrich Lehmann, email:

Keywords: myeloid neoplasms, next-generation sequencing, FFPE, MDS, hematopathology, Pathology Section

Received: February 02, 2016 Accepted: March 14, 2016 Published: March 23, 2016


Microscopic examination of myelodysplastic syndromes (MDS) and myelodysplastic-myeloproliferative neoplasms (MDS/MPN) may be challenging because morphological features can overlap with those of reactive states. Demonstration of clonal hematopoiesis provides a diagnostic clue and has become possible by comprehensive mutation profiling of a number of frequently mutated genes, some of them with large coding regions.

To emphasize the potential benefit of NGS in hematopathology we present sequencing results from routinely processed formalin-fixed and paraffin-embedded (FFPE) bone marrow trephines (n = 192). A customized amplicon-based gene panel including 23 genes frequently mutated in myeloid neoplasms was established and implemented. Thereby, 629,691 reads per sample (range 179,847–1,460,412) and a mean coverage of 2,702 (range 707–6,327) could be obtained, which are sufficient for comprehensive mutational profiling. Seven samples failed in sequencing (3.6%). In 185 samples we found in total 269 pathogenic variants (mean 1.4 variants per patient, range 0-5), 125 Patients exhibit at least one pathogenic mutation (67.6%). Variants show allele frequencies ranging from 6.7% up to 95.7%. Most frequently mutated genes were TET2 (28.7%), SRSF2 (19.5%), ASXL1 (8.6%) and U2AF1 (8.1%). The mutation profiling increases the diagnostic precision and adds prognostic information.

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