Somatic Point Mutations Are Prognostic in MDS Patients

Somatic gene mutations in bone marrow predicted how long patients with myelodysplastic syndromes (MDS) would live after diagnosis.

Benjamin Levine Ebert, MD, PhD, at Brigham and Women's Hospital (BWH; Boston, MA, USA) and colleagues used a combination of genomic approaches, including next-generation sequencing and mass spectrometry-based genotyping, to identify mutations in samples of bone marrow from 439 patients with MDS. They then examined whether the mutation status for each gene was associated with clinical variables and overall survival.

Nearly a third of the patients in the study had mutations in one or more of the five prognostic genes identified. Prior studies have suggested that mutations in individual genes can change the predicted prognosis of patients in MDS, but often included only a small number of patients or only considered mutations in a few genes.

Myelodysplastic syndromes are clinically heterogeneous disorders characterized by clonal hematopoiesis, impaired differentiation, peripheral-blood cytopenias, and a risk of progression to acute myeloid leukemia.

While some clinical variables are useful, current methods for predicting prognosis for individual patients are not ideal. Patients with the same clinical features can have very different outcomes from their disease.

The investigators hope to identify mutations that predict response to individual therapies. They expect that this genetic information will be used clinically as part of a novel prognostic scoring system and as predictors of therapeutic responses.

"In this study we identified mutations in several genes that predict a worse prognosis for patients than we would have expected using the most commonly used clinical scoring system (the International Prognostic Scoring System for MDS, or IPSS)," said Dr. Ebert.

Somatic point mutations are common in myelodysplastic syndromes and are associated with specific clinical features. Mutations in TP53, EZH2, ETV6, RUNX1, and ASXL1 are predictors of poor overall survival in patients with myelodysplastic syndromes, independently of established risk factors. If low risk patients had such mutations, physicians might decide to offer them more aggressive treatment or monitor them more closely.

The study was reported in the June 30, 2011, issue of the New England Journal of Medicine.

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