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Familial hematological malignancies: ASXL1 gene investigation

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.

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Acknowledgments

This work was supported by la Société Française d’Hématologie, le groupe Génétique et Cancer and Institut National du Cancer (INCa) and the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique en Tunisie. It is a part of the GenHem INSERM/DGRS project.

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Corresponding author

Correspondence to W. S. Hamadou.

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Ethical standards

This study was approved by the ethics committee of the hospital and all subjects gave their informed consent according to Helsinki Declaration.

Conflict of interest

We declare no conflict of interest.

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Cite this article

Hamadou, W.S., Abed, R.E., Besbes, S. et al. Familial hematological malignancies: ASXL1 gene investigation. Clin Transl Oncol 18, 385–390 (2016). https://doi.org/10.1007/s12094-015-1379-7

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Keywords

  • ASXL1 gene
  • Germline mutation
  • Familial hematological malignancies
  • Non-Hodgkin lymphoma