Regions of homozygosity confer a worse prognostic impact in myelodysplastic syndrome with normal karyotype

Abstract

Half of the myelodysplastic syndromes (MDS) have normal karyotype by conventional banding analysis. The percentage of true normal karyotype cases can be reduced by 20-30% with the complementary application of genomic microarrays. We here present a multicenter collaborative study of 163 MDS cases with a normal karyotype (≥10 metaphases) at diagnosis. All cases were analyzed with the ThermoFisher® microarray (either SNP 6.0 or CytoScan HD) for the identification of both copy number alteration(CNA) and regions of homozygosity (ROH). Our series supports that 25 Mb cut-off as having the most prognostic impact, even after adjustment by IPSS-R. This study highlights the importance of microarrays in MDS patients, to detect CNAs and especially to detect acquired ROH which has demonstrated a high prognostic impact.

Keywords: chromosome; cytogenetics; microarrays; molecular cytogenetics; myelodysplastic syndromes.

FIGURE 1

Circos plot displaying genetic aberrations found by microarrays. Blue bars indicate gains; red bars, losses; and green bars, regions of homozigosity.

FIGURE 2

(A) OS curve for the presence or absence of ROH alterations. (B) OS curve considering the presence of ROH greater than 25 Mb. (C) AML evolution considering the presence of ROH greater than 25 Mb. (D) OS curve, after IPSS‐R adjustment, for microarray result (normal vs. altered). (E) OS curve, after IPSS‐R adjustment, considering the presence of ROH greater than 25 Mb. Abbreviations: AML, acute myeloid leukemia; IPSS‐R, revised international prognostic scoring system; OS, overall survival; ROH, region of homozygosity.