1. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes
- Author
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Haferlach, T, Nagata, Y, Grossmann, V, Okuno, Y, Bacher, U, Nagae, G, Schnittger, S, Sanada, M, Kon, A, Alpermann, T, Yoshida, K, Roller, A, Nadarajah, N, Shiraishi, Y, Shiozawa, Y, Chiba, K, Tanaka, H, Koeffler, HP, Klein, H-U, Dugas, M, Aburatani, H, Kohlmann, A, Miyano, S, Haferlach, C, Kern, W, and Ogawa, S
- Subjects
Genetic Testing ,Clinical Research ,Rare Diseases ,Human Genome ,Genetics ,Biotechnology ,Cancer ,Hematology ,Adult ,Aged ,Aged ,80 and over ,Female ,Gene Frequency ,Genetic Association Studies ,Genetic Markers ,High-Throughput Nucleotide Sequencing ,Humans ,Male ,Middle Aged ,Mutation ,Mutation Rate ,Myelodysplastic Syndromes ,Polymorphism ,Single Nucleotide ,Prognosis ,Proportional Hazards Models ,Young Adult ,next-generation sequencing ,molecular markers ,myelodysplastic syndromes ,prognostic score ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology - Abstract
High-throughput DNA sequencing significantly contributed to diagnosis and prognostication in patients with myelodysplastic syndromes (MDS). We determined the biological and prognostic significance of genetic aberrations in MDS. In total, 944 patients with various MDS subtypes were screened for known/putative mutations/deletions in 104 genes using targeted deep sequencing and array-based genomic hybridization. In total, 845/944 patients (89.5%) harbored at least one mutation (median, 3 per patient; range, 0-12). Forty-seven genes were significantly mutated with TET2, SF3B1, ASXL1, SRSF2, DNMT3A, and RUNX1 mutated in >10% of cases. Many mutations were associated with higher risk groups and/or blast elevation. Survival was investigated in 875 patients. By univariate analysis, 25/48 genes (resulting from 47 genes tested significantly plus PRPF8) affected survival (P
- Published
- 2014