Targeted next-generation sequencing in myelodysplastic syndrome and chronic myelomonocytic leukemia aids diagnosis in challenging cases and identifies frequent spliceosome mutations in transformed acute myeloid leukemia

Erica Reinig, Fei Yang, Elie Traer, Ranjana Arora, Shari Brown, Rogan Rattray, Rita Braziel, Guang Fan, Richard Press, Jennifer Dunlap

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Objectives: Optimal integration of next-generation sequencing (NGS) into clinical practice in hematologic malignancies remains unclear. We evaluate the utility of NGS in myeloid malignancies. Methods: A 42-gene panel was used to sequence 109 cases of myelodysplastic syndrome (MDS, n=38), chronic myelomonocytic leukemia (CMML, n=14), myeloproliferative neoplasm (MPN, n=24), and MDS and/or MPN transformed to acute myeloid leukemia (AML, n=33). Results: At least one pathogenic mutation was identified in 74% of cases of MDS, 100% of CMMLs, and 96% of MPNs. In contrast, only 47% of cases of MDS (18/38) and 7% (1/14) of CMMLs exhibited abnormal cytogenetics. In diagnostically difficult cases of MDS or CMML with normal cytogenetics, NGS identified a pathogenic mutation and was critical in establishing the correct diagnosis. Spliceosomal genes and epigenetic modifiers were frequently mutated. Spliceosome mutations were also frequently detected in AML arising from MDS, CMML, or MPN (39%) compared with the reported rate in de novo AML (7%-14%). Conclusions: In difficult cases of MDS or MPN, NGS facilitates diagnosis by detection of gene mutations to confirm clonality, and AMLs evolving from MDS or MPN carry frequent mutations in spliceosomal genes.

Original languageEnglish (US)
Pages (from-to)497-506
Number of pages10
JournalAmerican journal of clinical pathology
Volume145
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Gene mutations
  • Leukemic transformation
  • Molecular hematopathology
  • Myelodysplastic syndrome
  • Myeloproliferative neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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