Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes
2015; Springer Nature; Volume: 30; Issue: 3 Linguagem: Inglês
10.1038/leu.2015.304
ISSN1476-5551
AutoresDavid A. Sallman, Rami S. Komrokji, Christine Vaupel, Thomas Cluzeau, Susan Geyer, Kathy L. McGraw, Najla H Al Ali, Jeffrey E. Lancet, Matthew J. McGinniss, Shareef Nahas, Alexander Smith, Austin Kulasekararaj, G J Mufti, Alan F. List, Jeff Hall, Eric Padron,
Tópico(s)Lymphoma Diagnosis and Treatment
ResumoAlthough next-generation sequencing has allowed for the detection of somatic mutations in myelodysplastic syndromes (MDS), the clinical relevance of variant allele frequency (VAF) for the majority of mutations is unknown. We profiled TP53 and 20 additional genes in our training set of 219 patients with MDS or secondary acute myeloid leukemia with findings confirmed in a validation cohort. When parsed by VAF, TP53 VAF predicted for complex cytogenetics in both the training (P=0.001) and validation set (P 40% had a median overall survival (OS) of 124 days versus an OS that was not reached in patients with VAF 40% was an independent covariate (HR, 1.61; P<0.0001). In addition, SRSF2 VAF predicted for monocytosis (P=0.003), RUNX1 VAF with thrombocytopenia (P=0.01) and SF3B1 with ringed sideroblasts (P=0.001). Together, our study indicates that VAF should be incorporated in patient management and risk stratification in MDS.
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