IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Identification of Genetic Variants in Myeloid Malignancies by Targeted Sequencing
Autor/es:
ZANELLA L; NOVICKAS A; AGRIELLO E; LINCANGO YUPANKI M; LARRIPA I; BENDER A; BELLI C; RAHHAL M; BORDONE J; ZUBIETA M
Reunión:
Congreso; LXV Reunion anual SAIC 2020; 2020
Institución organizadora:
SAIC, SAFIS y SAI
Resumen:
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 and 20-AML. Globally, 99 sequence variants were found mainly involving epigenetic regulators (37), transcription factors (18) and the splicing machinery (9). 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 sequence 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 0.48 in CMML patients, 0.44 in AML and 0.30 in MDS.Both panels include 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 involved in myeloid diseases.