Characterization of TP53 mutations in low-grade myelodysplastic syndromes and myelodysplastic syndromes with a non-complex karyotype.
OBJECTIVES
Although commonly associated with high-grade myelodysplastic syndrome (MDS) and MDS with a complex karyotype, TP53 mutations also occur in low-grade MDS and MDS with a non-complex karyotype. In latter cases, their clinicopathological features and the characteristics of TP53 mutations remain poorly characterized.


METHODS
176 MDS cases with TP53 mutations were stratified and characterized based on their karyotype and histologic subtype.


RESULTS
Among 176 cases, 17% had a non-complex karyotype and 24% were low-grade MDS. TP53 mutations often occurred in DNA-binding domains and the majority of cases had only one mutation, irrespective of their karyotype and MDS subtype. The variant allele frequency (VAF), however, was associated with karyotype complexity and the types of MDS with a lower VAF found in cases with a non-complex karyotype and low-grade MDS. A low (<20%) VAF was associated with a better survival, as well as low-grade subtype.


CONCLUSIONS
In low-grade MDS and MDS with a non-complex karyotype, TP53 mutations showed a lower VAF. Patients with a lower VAF had a better survival. TP53 mutations are not the only prognostic factor in MDS patients with TP53 mutations as the VAF, blast counts and history of prior therapy also play important roles in prognosis.
['Wang|Wei|W|http://orcid.org/0000-0001-6821-4556', 'Routbort|Mark J|MJ|', 'Tang|Zhenya|Z|', 'Ok|Chi Young|CY|', 'Patel|Keyur P|KP|', 'Daver|Naval|N|', 'Garcia-Manero|Guillermo|G|', 'Medeiros|L Jeffrey|LJ|', 'Wang|Sa A|SA|']
D000368:Aged D000369:Aged, 80 and over D004252:DNA Mutational Analysis D005260:Female D006801:Humans D059785:Karyotype D008297:Male D008875:Middle Aged D009154:Mutation D009190:Myelodysplastic Syndromes D016016:Proportional Hazards Models D012189:Retrospective Studies D016159:Tumor Suppressor Protein p53
TP53 myelodysplastic syndrome non-complex karyotype allele frequency survival