RESUMO
PURPOSE: Familial aggregation among patients with several hematological malignancies has been revealed. This emphasizes the importance of genetic factors. Only few genes predisposing to familial hematological malignancies have been reported until now due to the low occurrence. We have described in previous study PRF1 and CEBPA variants that might contribute to the background of genetic factors, which encourage us to extend our investigations to other cooperating genes. The aim of this study is to determine whether germline additional sex combs-like 1 (ASXL1) gene mutations may be involved? METHODS/PATIENTS: In this study, we investigated the candidate gene ASXL1 by direct sequencing in 88 unrelated Tunisian and French families with aggregated hematological malignancies. RESULTS: We report a new p.Arg402Gln germline missense substitution in two related Tunisian patients which has not been previously described. We identified here this variant for the first time in non-Hodgkin lymphoma. The p.Arg402Gln variant was not found in 200 control chromosomes. In silico analysis has predicted potential deleterious effect on ASXL1 protein. CONCLUSIONS: From an extended candidate genes analyzed in the field of familial hematological malignancies, ASXL1 might be involved. This variant should be considered since a potential damaging effect was predicted by in silico analysis, with a view to develop functional assay in order to investigate the biological assessment.
Assuntos
Biomarcadores Tumorais/genética , Mutação em Linhagem Germinativa/genética , Neoplasias Hematológicas/genética , Mutação de Sentido Incorreto/genética , Proteínas Repressoras/genética , Adulto , Sequência de Aminoácidos , Análise Mutacional de DNA , Feminino , Seguimentos , Predisposição Genética para Doença , Neoplasias Hematológicas/diagnóstico , Humanos , Masculino , Estadiamento de Neoplasias , Linhagem , Prognóstico , Homologia de Sequência de AminoácidosRESUMO
1. The distribution of tissue kallikrein in the rat brain was investigated by an immunohistochemical technique using antiserum against rat urinary kallikrein. The kallikrein-immunoreactive cells were widespread and scattered in both the cerebral cortex and brain stem, and the immunoreactive substance appeared to be preferentially localized around the neuronal cell body and their processes. 2. Furthermore, in order to define whether brain kallikrein levels vary in the aging process, the hydrolyzing activity in the cerebrum L-prolyl-L-phenylalanyl-L-arginine-4-methyl-coumaryl-7-amide (Pro-Phe-Arg-MCA) was measured in young (7-week old) and old (36-week old) female senescence accelerated mice (SAM-P/8 and SAM-R/1). The brain kallikrein levels of 7- as well as 36-week old SAM-P/8 were found to be lower than those of 7-week old SAM-R/1 (a control strain). Also, the brain kallikrein level of 36-week old SAM-R/1 animals was markedly reduced when compared with the 7-week old mice, suggesting that the reduced amount of cerebral kallikrein reflects the aging of the brain.