Shallow whole-genome sequencing of bone marrow aspirates in myelodysplastic neoplasms: A retrospective comparison with cytogenetics.

Copy number alterations (CNA) are powerful prognostic markers in myelodysplastic neoplasms (MDS) and are routinely analyzed by conventional cytogenetic analysis (CCA) on bone marrow (BM). Although CCA is still the gold standard, it requires extensive hands-on time and highly trained staff for the analysis, making it a laborious technique. To reduce turn-around-time per case, shallow whole genome sequencing (sWGS) technologies offer new perspectives for the diagnostic work-up of this disorder. We compared sWGS with CCA for the detection of CNAs in 33 retrospective BM samples of patients with MDS. Using sWGS, CNAs were detected in all cases and additionally allowed the analysis of three cases for which CCA failed. The prognostic stratification (IPSS-R score) of 27 out of 30 patients was the same with both techniques. In the remaining cases, discrepancies were caused by the presence of balanced translocations escaping sWGS detection in two cases, a subclonal aberration reported with CCA that could not be confirmed by FISH or sWGS, and the presence of an isodicentric chromosome idic(17)(p11) missed by CCA. Since sWGS can almost entirely be automated, our findings indicate that sWGS is valuable in a routine setting validating it as a cost-efficient tool.