IDENTIFICATION OF SINGLE NUCLEOTIDE VARIANTS AND FUSION GENES THROUGH TRANSCRIPTOMICS OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS FROM A MULTICENTER CLINICAL STUDY IN ARGENTINA

RUIZ, MARÍA SOL; ABBATE, MERCEDES; AVEDAÑO, DANIEL; RICCHERI, CECILIA; VAZQUEZ, ELBA; GUERON, GERALDINE; COTIGNOLA, JAVIER

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2022

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Patients diagnosed with Acute Lymphoblastic Leukemia (ALL) are stratified into risk groups based on biochemical, cytogenetic and molecular signatures. While considerable progress has been made on treatment efficacy and survival rates, relapse is the most important cause for treatment failure and occurs in about 15-30% of patients. In approximately one-third of B-ALL patients, major pathogenic molecular abnormalities have yet to be identified. Aims: to characterize molecular profiles associated with disease outcome and improve molecular classification of ALL patients from Argentina. Methods: we studied single nucleotide variants and fusion genes in 39 pediatric ALL patients that are part of a national multicenter clinical protocol (ALL IC GATLA 2010), through transcriptome sequencing of bone marrow samples at diagnosis. RNAmut software was used to evaluate SNVs/InDels in 114 selected genes and 79 selected fusion genes in RNAseq data. Discovery of fusion genes was complemented with STAR-Fusion software. Variants were analyzed and filtered based on an in-house pipeline. Variants were assessed in silico through Variant Effect Predictor, OncoKB, Varsite, ProteinPaint and COSMIC-3D. Confirmation was performed by RT-PCR and Sanger sequencing. Results: We found a total of 9,594 variants. After annotation and filtering, 20 SNVs/InDels were identified in 11/34 patients (32.3%). Variants that had not been previously described in ALL were found in CREBBP, CSF3R, ETV6, TP53, ATM and DUX4. The group of patients harboring point mutations had significantly lower relapse-free survival (p