Resumo

SLAVUTSKY, Irma; GALVANO, Camila; SANTOS, Patricia Dos  e  STANGANELLI, Carmen. NOTCH1 gene mutations in chronic lymphocytic leukemia. Salud(i)Ciencia [online]. 2019, vol.23, n.4, pp.1-9. ISSN 1667-8682.  http://dx.doi.org/www.dx.doi.org/10.21840/siic/159835.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. The disease has a highly variable clinical course, ranging from very indolent cases to patients with aggressive and rapidly progressing outcome. Genetic studies are useful tools in the analysis of this pathology, and are incorporated in international risk classifications. The analysis of genomic rearrangements and the mutational status of immunoglobulin heavy chain variable have allowed risk groups of high prognostic value to be established. More recently, next generation sequencing studies have identified novel somatic mutations that could explain the wide clinical variability of this pathology. Among them, the analysis of NOTCH1 (neurogenic locus notch homolog protein 1) gene mutations are of interest, as deregulation is associated with tumorigenesis. NOTCH1 mutations are mostly located at exon 34 (80% of cases) and 3´UTR (untranslated region). They produce premature stop codons that produce a constitutively active and stable NOTCH1 protein. NOTCH1 mutations are associated with adverse prognosis and refractoriness to treatment. The aim of this study was to analyze NOTCH1 mutations in CLL patients by ASO-PCR and sequencing. Our results found 4.4% of cases with NOTCH1 mutated values concordant with international observations (5%-10%). Including them in the genetic status of CLL patients allows the characterization of risk groups, an aspect of great importance in clinical practice and therapeutic decisions, to be refined.

Palavras-chave : NOTCH1 gene; mutations; chronic lymphocytic leukemia; cytogenetics, FISH, IgH.

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