TY - JOUR
T1 - 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
AU - Reinig, Erica
AU - Yang, Fei
AU - Traer, Elie
AU - Arora, Ranjana
AU - Brown, Shari
AU - Rattray, Rogan
AU - Braziel, Rita
AU - Fan, Guang
AU - Press, Richard
AU - Dunlap, Jennifer
N1 - Publisher Copyright:
© American Society for Clinical Pathology, 2016.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Gene mutations
KW - Leukemic transformation
KW - Molecular hematopathology
KW - Myelodysplastic syndrome
KW - Myeloproliferative neoplasms
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U2 - 10.1093/AJCP/AQW016
DO - 10.1093/AJCP/AQW016
M3 - Article
C2 - 27124934
AN - SCOPUS:84981166164
SN - 0002-9173
VL - 145
SP - 497
EP - 506
JO - American journal of clinical pathology
JF - American journal of clinical pathology
IS - 4
ER -