دورية أكاديمية
أعرض في EDS

Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes.

التفاصيل البيبلوغرافية
العنوان: Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes.
المؤلفون: Cedena MT; Hematology Department, Hospital Universitario 12 Octubre, CNIO, Universidad Complutense, Madrid, Spain.; Research Institute of Hospital 12 de Octubre ('i+12'), Madrid, Spain., Rapado I; Hematology Department, Hospital Universitario 12 Octubre, CNIO, Universidad Complutense, Madrid, Spain.; Research Institute of Hospital 12 de Octubre ('i+12'), Madrid, Spain., Santos-Lozano A; Research Institute of Hospital 12 de Octubre ('i+12'), Madrid, Spain.; GIDFYS, European University Miguel de Cervantes, Valladolid, Spain., Ayala R; Hematology Department, Hospital Universitario 12 Octubre, CNIO, Universidad Complutense, Madrid, Spain.; Research Institute of Hospital 12 de Octubre ('i+12'), Madrid, Spain., Onecha E; Hematology Department, Hospital Universitario 12 Octubre, CNIO, Universidad Complutense, Madrid, Spain.; Research Institute of Hospital 12 de Octubre ('i+12'), Madrid, Spain., Abaigar M; IBSAL, Cancer Research Center (USAL-CSIC), Salamanca, Spain., Such E; Hematology Department, Hospital Universitario La Fe, Valencia, Spain., Ramos F; Hematology Department, Hospital Universitario de León, and IBIOMED, Universidad León, León, Spain., Cervera J; Hematology Department, Hospital Universitario La Fe, Valencia, Spain.; Genetics Unit, Hospital Universitario La Fe, Valencia, Spain., Díez-Campelo M; IBSAL, Cancer Research Center (USAL-CSIC), Salamanca, Spain.; Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain., Sanz G; Hematology Department, Hospital Universitario La Fe, Valencia, Spain., Rivas JH; IBSAL, Cancer Research Center (USAL-CSIC), Salamanca, Spain.; Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain., Lucía A; Research Institute of Hospital 12 de Octubre ('i+12'), Madrid, Spain.; Universidad Europea de Madrid, Madrid, Spain., Martínez-López J; Hematology Department, Hospital Universitario 12 Octubre, CNIO, Universidad Complutense, Madrid, Spain.; Research Institute of Hospital 12 de Octubre ('i+12'), Madrid, Spain.
المصدر: Oncotarget [Oncotarget] 2017 Oct 27; Vol. 8 (63), pp. 106948-106961. Date of Electronic Publication: 2017 Oct 27 (Print Publication: 2017).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: eCollection Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Albany, N.Y. : Impact Journals
مستخلص: We evaluated the association of mutations in 34 candidate genes and response to azacitidine in 84 patients with myelodysplastic syndrome (MDS), with 217 somatic mutations identified by next-generation sequencing. Most patients (93%) had ≥1 mutation (mean=2.6/patient). The overall response rate to azacitidine was 42%. No clinical characteristic was associated with response to azacitidine. However, total number of mutations/patient was negatively associated with overall drug response (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.33-0.94; p=0.028), and a positive association was found for having ≥1 mutation in a DNA methylation-related gene: TET2, DNMT3A, IDH1 and/or IDH2 (OR: 4.76, 95%CI: 1.31-17.27; p=0.017). Mutations in TP53 (hazard ratio [HR]: 3.88; 95%CI: 1.94-7.75) and EZH2 (HR: 2.50; 95%CI: 1.23-5.09) were associated with shorter overall survival. Meta-analysis of 6 studies plus present data (n=815 patients) allowed assessment of the association of drug response with mutations in 9 candidate genes: ASXL1, CBL, EZH2, SF3B1, SRSF2, TET2, DNMT3A, IDH1/2 and TP53. TET2 mutations predicted a more favorable drug response compared with 'wild-type' peers (pooled OR: 1.67, 95%CI: 1.14-2.44; p=0.01). In conclusion, mutations in the DNA methylation pathway, especially TET2 mutations, and low number of total mutations are associated with a better response to azacitidine.
Competing Interests: CONFLICTS OF INTEREST FR: honoraria or consultation fees: Celgene, Janssen, Amgen, Novartis, Pfizer, Glaxo-Smith-Kline, Merck-Sharp & Dohme. The remaining authors declare no conflict of interest.
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فهرسة مساهمة: Keywords: hypomethylating agents; mutational profile; myelodysplastic syndromes; next generation sequencing
تواريخ الأحداث: Date Created: 20180102 Latest Revision: 20191120
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC5739787
DOI: 10.18632/oncotarget.22157
PMID: 29291002
قاعدة البيانات: MEDLINE
الوصف
تدمد:1949-2553
DOI:10.18632/oncotarget.22157