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Somatic Mutations Common in Myelodysplastic Syndromes

Mutations in five genes independently associated with prediction of poor overall survival rate

THURSDAY, June 30 (HealthDay News) -- Somatic point mutations are frequently found in myelodysplastic syndromes, and may be correlated with specific clinical features, according to a study published in the June 30 issue of the New England Journal of Medicine.

Rafael Bejar, M.D., Ph.D., from the Harvard Medical School in Boston, and colleagues investigated the presence of somatic mutations in cancer-associated genes in patients with myelodysplastic syndromes. Bone marrow samples from 439 patients were assessed for mutations using genomic approaches, including next-generation sequencing and mass spectrometry-based genotyping. The association of each gene mutation with clinical variables, including specific cytopenias, the proportion of blasts, and overall survival was analyzed.

The investigators identified 18 genes with mutations, including two, ETV6 and GNAS, that had not previously been reported in myelodysplastic syndromes. At least one point mutation was seen in 51 percent of all patients, including 52 percent of the patients with normal cytogenetics. Severe thrombocytopenia and an increased proportion of bone marrow blasts were significantly associated with mutations in RUNX1, TP53, and NRAS. The presence of mutations in five genes offered independent significant prognosis for death from any cause: TP53 (hazard ratio [HR], 2.48), EZH2 (HR, 2.13), ETV6 (HR, 2.04), RUNX1 (HR, 1.47), and ASXL1 (HR, 1.38).

"Somatic mutations in several genes are associated with distinct effects on cytopenias, blast proportion, the likelihood of co-occurrence with other molecular lesions, and overall survival," the authors write.

Several authors disclosed financial relationships with the pharmaceutical industry.

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