W S Hamadou1, R E Abed2, S Besbes2, V Bourdon3, A Fabre3, Y B Youssef2,4, M A Laatiri5, F Eisinger6, V Mari7, P Gesta8, H Dreyfus9, V Bonadona10, C Dugast11, H Zattara12, L Faivre13, S Y Jemni14, T Noguchi3, A Khélif2,4, H Sobol3, Z Soua2. 1. UR "Biologie moléculaire des leucémies et lymphomes", Laboratoire de Biochimie, Faculté de Médecine de Sousse, Université de Sousse, Avenue Mohamed Karoui, 4000, Sousse, Tunisia. walid_sabrimail@yahoo.fr. 2. UR "Biologie moléculaire des leucémies et lymphomes", Laboratoire de Biochimie, Faculté de Médecine de Sousse, Université de Sousse, Avenue Mohamed Karoui, 4000, Sousse, Tunisia. 3. Département d'Oncologie Génétique, de Prévention et Dépistage, Institut Paoli-Calmettes, Marseille, France. 4. Service d'Hématologie clinique, CHU Farhat Hached, Sousse, Tunisia. 5. Service d'Hématologie clinique, CHU Fattouma Bourguiba, Monastir, Tunisia. 6. Département d'Anticipation et de Suivi du Cancer, Centre de Lutte Contre le Cancer - Institut Paoli Calmettes, Marseille, France. 7. Service d'Oncologie Génétique, Centre de Lutte Contre le Cancer - Centre Antoine Lacassagne, Nice, France. 8. Service d'Oncologie Génétique, Centre Hospitalier, Niort, France. 9. Institut Sainte Catherine, Avignon, France. 10. Unité de génétique Epidémiologique, Centre Léon Bérard, Lyon, France. 11. Centre Eugène Marquis, Rennes, France. 12. Département de Génétique, Hôpital de la Timone, Marseille, France. 13. Hôpital d'Enfants, CHU de Dijon, Dijon, France. 14. Centre régional de transfusion sanguine. CHU F. Hached, Sousse, Tunisia.
Abstract
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.
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.
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