Yazarlar : Bejar R, Stevenson K, Caughey B et al

Yayın : J Clin Oncol

Yayın Yılı : 2014

Pubmed Linki : http://www.docguide.com/somatic-mutations-predict-poor-outcome-patients-myelodysplastic-syndrome-after-hematopoietic-stem-ce?tsid=5

Konu : MDS

Literatür İçeriği :  PURPOSE Recurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known.

PATIENTS AND METHODS We used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.

RESULTS Mutations were identified in 92% of patients, most frequently in the ASXL1 (29%), TP53 (21%), DNMT3A (18%), and RUNX1 (16%) genes. In univariable analyses, only TP53 mutations were associated with shorter overall (OS; hazard ratio [HR], 3.74; P<.001) and progression-free survival (HR, 3.97; P<.001). After adjustment for clinical variables associated with these end points, mutations in TP53 (HR, 2.30; P = .027), TET2 (HR, 2.40; P = .033), and DNMT3A (HR, 2.08; P = .049) were associated with decreased OS. In multivariable analysis including clinical variables, complex karyotype status, and candidate genes, mutations in TP53 (HR, 4.22; P ≤ .001) and TET2 (HR, 1.68; P = .037) were each independently associated with shorter OS. Nearly one half of patients (46%) carried a mutation in TP53, DNMT3A, or TET2 and accounted for 64% of deaths. Three-year OS in patients without these mutations was 59% (95% CI, 43% to 72%), versus 19% (95% CI, 9% to 33%) in patients with these mutations.

CONCLUSION Mutations in TP53, TET2, or DNMT3A identify patients with MDS with shorter OS after HSCT.

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