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
| Autor: | Erica Reinig, Rogan Rattray, Elie Traer, Rita M. Braziel, Fei Yang, Shari L. Brown, Richard D. Press, Guang Fan, Ranjana Arora, Jennifer Dunlap |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male medicine.medical_specialty Myeloid Adolescent DNA Mutational Analysis Chronic myelomonocytic leukemia Gene mutation Biology medicine.disease_cause Young Adult 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Humans Child Myeloproliferative neoplasm Aged Aged 80 and over Mutation Cytogenetics High-Throughput Nucleotide Sequencing Myeloid leukemia Leukemia Myelomonocytic Chronic General Medicine Middle Aged medicine.disease Leukemia Myeloid Acute Leukemia medicine.anatomical_structure Child Preschool Myelodysplastic Syndromes 030220 oncology & carcinogenesis Immunology Spliceosomes Cancer research Female 030215 immunology |
| Zdroj: | American Journal of Clinical Pathology. 145:497-506 |
| ISSN: | 1943-7722 0002-9173 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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