Whole exome sequencing or pan-myeloid NGS gene panel to assess leukemic evolution of myelodysplastic syndromes: advantages and disadvantages

NGS gene panels interrogating few genes clinically relevant for a specific disease are being extensively used for diagnosis, prognosis, and treatment. However, when panel results are inconclusive, some laboratories recommend the use of Whole Exome sequencing (WES), or WES is even offered as the first technique to genetically assess patient condition. In this short communication we report a comparison of WES and a myeloid NGS gene panel data from 16 samples of 8 cases with Myelodysplastic Syndromes (MDS) that evolved to Acute Myeloid Leukemia (AML), addressing their advantages and disadvantages from both technical and clinical point of view. On the one hand, our data show a loss of clinically relevant variants sequenced with WES that were indeed called by the NGS panel at a low Variant Allele Frequency (VAF); this finding was not surprising since WES was sequenced at an average depth of 250x, while the NGS panel was sequenced at an average depth of 4500X. On the other hand, WES called a likely pathogenic variant in GNAS p. Arg844Cys, missed by the panel due to design constraints. Therefore, based in our data, both techniques were complementary and therefore potentially clinically valuable: WES for the discovery of new variants, and NGS gene panels for the detection of emerging clones, which gives a more precise image of the tumor clonal heterogeneity.