BUSCADOR RECOLECTA

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., This work was funded by ISCIII (Ministerio de Economía y
Competitividad of Spanish central government, grant number
PI16/00159) and supported by CIMA LAB Diagnostics research program.
AAD is supported by a CIMA ¿s fellowship; MFM is supported
by the Spanish Association against Cancer (AECC, AIO2014).

The landscape of medical sequencing has rapidly changed with the evolution of next generation sequencing (NGS). These technologies have contributed to the molecular characterization of the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), through the identification of recurrent gene mutations, which are present in >80% of patients. These mutations contribute to a better classification and risk stratification of the patients. Currently, clinical laboratories include NGS genomic analyses in their routine clinical practice, in an effort to personalize the diagnosis, prognosis and treatment of MDS and CMML. NGS technologies have reduced the cost of large-scale sequencing, but there are additional challenges involving the clinical validation of these technologies, as continuous advances are constantly being made. In this context, it is of major importance to standardize the generation, analysis, clinical interpretation and reporting of NGS data. To that end, the Spanish MDS Group (GESMD) has expanded the present set of guidelines, aiming to establish common quality standards for the adequate implementation of NGS and clinical interpretation of the results, hoping that this effort will ultimately contribute to the benefit of patients with myeloid malignancies.