Oncotarget

Research Papers:

TP53 mutation variant allele frequency is a potential predictor for clinical outcome of patients with lower-risk myelodysplastic syndromes

Monika Belickova _, Jitka Vesela, Anna Jonasova, Barbora Pejsova, Hana Votavova, Michaela Dostalova Merkerova, Zuzana Zemanova, Jana Brezinova, Dana Mikulenkova, Marie Lauermannova, Jan Valka, Kyra Michalova, Radana Neuwirtova and Jaroslav Cermak

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Oncotarget. 2016; 7:36266-36279. https://doi.org/10.18632/oncotarget.9200

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Abstract

Monika Belickova1, Jitka Vesela1, Anna Jonasova2, Barbora Pejsova1, Hana Votavova1, Michaela Dostalova Merkerova1, Zuzana Zemanova3, Jana Brezinova1, Dana Mikulenkova1, Marie Lauermannova1, Jan Valka1, Kyra Michalova1,3, Radana Neuwirtova2, Jaroslav Cermak1

1Institute of Hematology and Blood Transfusion, Prague, Czech Republic

2First Department of Medicine, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic

3Center of Oncocytogenetics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic

Correspondence to:

Monika Belickova, email: [email protected]

Keywords: myelodysplastic syndrome, mutational status, TP53, prognosis, variant allele frequency

Received: January 03, 2016     Accepted: April 16, 2016     Published: May 06, 2016

ABSTRACT

TP53 mutations are frequently detected in patients with higher-risk myelodysplastic syndromes (MDS); however, the clinical impact of these mutations on the disease course of patients with lower-risk MDS is unclear. In this study of 154 lower-risk MDS patients, TP53 mutations were identified in 13% of patients, with prevalence in patients with del(5q) (23.6%) compared to non-del(5q) (3.8%). Two-thirds of the mutations were detected at the time of diagnosis, and one-third were detected during the course of the disease. Multivariate analysis demonstrated that a TP53 mutation was the strongest independent prognostic factor for overall survival (OS) (HR: 4.39) and progression-free survival (PFS) (HR: 3.74). Evaluation of OS determined a TP53 variant allele frequency (VAF) threshold of 6% as an optimal cut-off for patient stratification. The median OS was 43.5 months in patients with mutations detected at the time of diagnosis and a mutational burden of > 6% VAF compared to 138 months (HR 12.2; p = 0.003) in patients without mutations; similarly, the median PFS was 20.2 months versus 116.6 months (HR 79.5; p < 0.0001). In contrast, patients with a mutational burden of < 6% VAF were stable for long periods without progression and had no significant impact on PFS or OS. Additionally, we found a high correlation in the mutational data from cells of the peripheral blood and those of the bone marrow, indicating that peripheral blood is a reliable source for mutation monitoring. Our results indicate that the clinical impact of TP53 mutations in lower-risk MDS patients depends on the level of mutational burden.


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