Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts

• Published in: The New England journal of medicine Vol. 365; no. 15; pp. 1384 - 1395
• Main Authors: Papaemmanuil, E, Cazzola, M, Boultwood, J, Malcovati, L, Vyas, P, Bowen, D, Pellagatti, A, Wainscoat, J.S, Hellstrom-Lindberg, E, Gambacorti-Passerini, C, Godfrey, A.L, Rapado, I, Cvejic, A, Rance, R, McGee, C, Ellis, P, Mudie, L.J, Stephens, P.J, McLaren, S, Massie, C.E, Tarpey, P.S, Varela, I, Nik-Zainal, S, Davies, H.R, Shlien, A, Jones, D, Raine, K, Hinton, J, Butler, A.P, Teague, J.W, Baxter, E.J, Score, J, Galli, A, Della Porta, M.G, Travaglino, E, Groves, M, Tauro, S, Munshi, N.C, Anderson, K.C, El-Naggar, A, Fischer, A, Mustonen, V, Warren, A.J, Cross, N.C.P, Green, A.R, Futreal, P.A, Stratton, M.R, Campbell, P.J
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 13.10.2011
• Subjects: Biological and medical sciences; Bone marrow; Deoxyribonucleic acid; DNA; Erythrocytes - pathology; Exons; Gene Expression Profiling; General aspects; Genetic testing; Genomes; Hematologic and hematopoietic diseases; High-Throughput Nucleotide Sequencing; Humans; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Medicin och hälsovetenskap; Mitochondria; mRNA; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Pathogenesis; Phenotype; Phosphoproteins - genetics; Point Mutation; Ribonucleoprotein, U2 Small Nuclear - genetics; RNA Splicing Factors; Sideroblasts; Splicing factors; Statistical analysis; Somatic mutation; Medicine; Ring; Malignant hemopathy; Sideroblast; Myelodysplastic syndrome; Cancer
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1103283

Abnormalities in a gene encoding a messenger RNA splicing enzyme were found in nearly two thirds of patients with myelodysplastic syndromes characterized by ring sideroblasts. Patients with mutations had improved survival as compared with those without mutations. The myelodysplastic syndromes are a heterogeneous group of hematologic cancers characterized by low blood counts, most commonly anemia, and a risk of progression to acute myeloid leukemia. 1 These disorders have increased in prevalence and are expected to continue to do so. Blood films and bone marrow–biopsy specimens from patients with myelodysplastic syndromes show dysplastic changes in myeloid cells, with abnormal proliferation and differentiation of one or more lineages. Target genes of recurrent chromosomal aberrations have been mapped, 2 , 3 and several genes have been identified as recurrently mutated in these disorders, including NRAS (encoding neuroblastoma RAS viral oncogene homologue), TP53 (encoding . . .