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Mutational analysis of TP53 gene in Tunisian familial hematological malignancies and sporadic acute leukemia cases

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Abstract

Mutations are responsible for familial cancer syndromes which account for approximately 5–10 % of all types of cancers. Familial cancers are often caused by genetic alterations occurring either in tumor suppressor or genomic stability genes such as TP53. In this study, we have analyzed the TP53 gene by direct sequencing approach, in a panel of 18 Tunisian familial hematological malignancies cases including several forms of leukemia, lymphoma and myeloid syndrome and 22 cases of sporadic acute leukemia. In one familial case diagnosed with acute lymphoblastic leukemia, we reported an intronic substitution 559+1 G>A which may disrupt the splice site and impact the normal protein function. Most of the deleterious mutations (Arg158His; Pro282Trp; Thr312Ser) as classified by IARC data base, were commonly reported in ALL cases studied here. The cosegregation of the two variants rs1042522 and rs1642785 was observed in most patients which may be in favor of the presence of linkage disequilibrium. The most defined TP53 mutations found here were identified in acute lymphoblastic leukemia context whereas only 3 % of mutations have been in previous studies. The cosegregation of the two recurrent variant rs1042522 and rs1642785 should be further confirmed.

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Acknowledgments

This work was supported by the Ministère de l’Enseignement Supérieur, de la Recherche Scientifique et des Technologies de l’Information et de la Communication en Tunisie. It is a part of the GenHem INSERM/DGRS project. We are grateful for English correction provided by Helmi Ben AZIZA.

Authors’ contributions

W.S.H., S.B., and V.B. conceived the study and performed the experiments and wrote the manuscript, Y.B.Y. and M.A.L. provides simple and clinical data, T.N. analyzed the data, A. K., H.S. and Z. S. supervised the project.

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Authors and Affiliations

  1. RU “Molecular Biology of Leukemias and Lymphomas”, Laboratory of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, Avenue Mohamed Karoui, 4000, Sousse, Tunisia

    Walid Sabri Hamadou, Sawsen Besbes & Zohra Soua

  2. Department of Genetic Oncology, Prevention and Screening, Institute Paoli-Calmettes, Marseille, France

    Violaine Bourdon, Testsuro Noguchi & Hagay Sobol

  3. Service of Clinical Hematology, CHU Farhat Hached, Sousse, Tunisia

    Yosra Ben Youssef & Abderrahim Khélif

  4. Service of Clinical Hematology, CHU Fattouma Bourguiba, Monastir, Monastir, Tunisia

    Mohamed Adnène Laatiri

Authors
  1. Walid Sabri Hamadou
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  2. Sawsen Besbes
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  3. Violaine Bourdon
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  4. Yosra Ben Youssef
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  5. Mohamed Adnène Laatiri
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  6. Testsuro Noguchi
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  7. Abderrahim Khélif
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  8. Hagay Sobol
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  9. Zohra Soua
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Correspondence to Walid Sabri Hamadou.

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Hamadou, W.S., Besbes, S., Bourdon, V. et al. Mutational analysis of TP53 gene in Tunisian familial hematological malignancies and sporadic acute leukemia cases. Familial Cancer 16, 153–157 (2017). https://doi.org/10.1007/s10689-016-9931-3

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  • DOI: https://doi.org/10.1007/s10689-016-9931-3

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