IDENTIFICATION OF GENETIC VARIANTS IN MYELOID MALIGNANCIES BY TARGETED SEQUENCING

RAHHAL, M.; BORDONE, J.; ZUBIETA, M.; ZANELLA, L.; NAVICKAS, A.; AGRIELLO, E.; LINCANGO, MARCO; LARRIPA, IRENE.; BENDER, A.; BELLI, CAROLINA.

Congreso; Reunion Anual de Sociedades de Biociencias; 2020

Next Generation Sequencing (NGS) technology has provided powerful tools to identify genetic variants with a high sensitivity in myeloid malignancies. However, it has not been widely adopted due to difficulties with health insurance coverage.Our aim was to describe pathogenic variants associated with myeloid malignancies detected by targeted sequencing approaches in two institutions of our media.Sequencing was performed in an Illumina platform using amplicon-based targeted sequencing (Illumina Ampliseq Myeloid Panel-Hospital El Cruce, Florencio Varela) and hybrid capture-based sequencing (Customized Panel, SOPHiA Genetics- Laboratorio de Especialidades Bioquímicas, Bahía Blanca), to screen 40 and 30 genes, respectively.A total of 43 patients were evaluated (16-MDS, 7-CMML, 20-AML) and 99 sequence variants were found (37 in epigenetic regulators, 22 in transcription factors, 22 in signaling pathways, 10 in splicing factors, 6 in damage repair and 2 in cohesins). Seven MDS patients presented 10 affected genes accumulating 17 nucleotide variants with a media of 2 (1-5) mutated genes and 2 (1-7) sequence variants/patient. CMML patients presented 27 variants in 14 genes with a media of 3 (2-4) affected genes and 4 (2-5) variants/patient. The AML cohort had a media of 2 (1-5) mutated genes and 3 (1-6) variants/patient, adding 55 variants in 20 genes. TET2 was the most compromised in MDS (4/17) and CMML (11/27), while in AML it was DNMT3A (7/55). The median VAF was 0.47 in CMML, 0.41 in AML and 0.25 in MDS.Both panels comprised the most relevant genes and allowed the identification of pathogenic variants in 84% of patients with myeloid malignancies. CMML displayed a higher media of variants with a higher VAF and a prevalence of TET2, while the number of affected genes was increased in AML. Sequence-based genetic tests provide useful information, not only at clinical level, but to improve the description of altered genes and pathways in myeloid diseases.