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Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation.


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

SUBMITTER: Bejar R 

PROVIDER: S-EPMC4207878 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation.

Bejar Rafael R   Stevenson Kristen E KE   Caughey Bennett B   Lindsley R Coleman RC   Mar Brenton G BG   Stojanov Petar P   Getz Gad G   Steensma David P DP   Ritz Jerome J   Soiffer Robert R   Antin Joseph H JH   Alyea Edwin E   Armand Philippe P   Ho Vincent V   Koreth John J   Neuberg Donna D   Cutler Corey S CS   Ebert Benjamin L BL  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20140804 25


<h4>Purpose</h4>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.<h4>Patients and methods</h4>We used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MD  ...[more]

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