Introduction The role of single mutations has been extensively studied myelodysplastic syndromes (MDS), but the impact of genetic aberrations in the context of other mutations is less well understood. BCOR is an epigenetic transcriptional corepressor. In MDS, BCOR mutations are rare and certain mutations are associated with poor prognosis. Our aim was to investigate the role of concurrent mutations in epigenetic MDS-driver genes in BCOR-mutated MDS. We hypothesised that these would be redundant and would not contribute to worse prognosis.
Methods Internal Next Generation Sequencing (NGS) database with targeted genetic profiling of >4000 tumor cases was queried to locate cases of MDS with BCL6 Corepressor protein (BCOR) mutations only (pBCOR) and cBCOR (comutated epigenetic modulators: TET2, ASXL1, DNMT3A, EZH2, IDH2, IDH1, BCORL1, ATRX). Overall survival was determined by chart review. Fischer’s exact test and unpaired t-test was performed for statistical analysis.
Results 25 patients with cBCOR were detected. Only five MDS patients with pBCOR were found. The number of patients with comutations (cBCOR) in epigenetic modulators comprised TET2 (n=5), ASXL1 (n=9), DNMT3A (n=11), EZH2 (n=2), IDH2 (n=4), IDH1 (n=1), BCORL1 (n=3), ATRX (n=1). cBCOR overall survival was 23.8 months versus 11.8 months for pBCOR group.
Conclusions In this study, we confirm the rarity of BCOR mutations. Our results show that there is a trend towards poorer prognosis in patient with pBCOR versus cBCOR although statistical significance was not reached. This may be due to enrichment of poor cytogenetics in pBCOR or increased responsiveness to hypomethylating agents in cBCOR. Larger studies are needed to validate our data.
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Handling editor Mary Frances McMullin.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
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