Mutational analysis of TP53 gene in Tunisian familial hematological malignancies and sporadic acute leukemia cases.
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.
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_sabrimail@yahoo.fr.
Walid Sabri
WS
Hamadou
RU "Molecular Biology of Leukemias and Lymphomas", Laboratory of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, Avenue Mohamed Karoui, 4000, Sousse, Tunisia.
Sawsen
S
Besbes
Department of Genetic Oncology, Prevention and Screening, Institute Paoli-Calmettes, Marseille, France.
Violaine
V
Bourdon
Service of Clinical Hematology, CHU Farhat Hached, Sousse, Tunisia.
Yosra Ben
YB
Youssef
Service of Clinical Hematology, CHU Fattouma Bourguiba, Monastir, Monastir, Tunisia.
Mohamed Adnène
MA
Laatiri
Department of Genetic Oncology, Prevention and Screening, Institute Paoli-Calmettes, Marseille, France.
Testsuro
T
Noguchi
Service of Clinical Hematology, CHU Farhat Hached, Sousse, Tunisia.
Abderrahim
A
Khélif
Department of Genetic Oncology, Prevention and Screening, Institute Paoli-Calmettes, Marseille, France.
Hagay
H
Sobol
RU "Molecular Biology of Leukemias and Lymphomas", Laboratory of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, Avenue Mohamed Karoui, 4000, Sousse, Tunisia.
Zohra
Z
Soua
D004252:DNA Mutational Analysis; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014416:Tunisia
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
Acute lymphoblastic leukemia; Acute myeloid leukemia; Familial hematological malignancies; TP53 gene mutations