Hamadou Walid Sabri, Besbes Sawsen, Bourdon Violaine, Youssef Yosra Ben, Laatiri Mohamed Adnène, Noguchi Testsuro, Khélif Abderrahim, Sobol Hagay, Soua Zohra
RU "Molecular Biology of Leukemias and Lymphomas", Laboratory of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, Avenue Mohamed Karoui, 4000, Sousse, Tunisia.
Department of Genetic Oncology, Prevention and Screening, Institute Paoli-Calmettes, Marseille, France.
Fam Cancer. 2017 Jan;16(1):153-157. doi: 10.1007/s10689-016-9931-3.
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.
突变是导致家族性癌症综合征的原因，家族性癌症综合征约占所有癌症类型的5%-10%。家族性癌症通常由肿瘤抑制基因或基因组稳定性基因（如TP53）发生的基因改变引起。在本研究中，我们采用直接测序方法分析了18例突尼斯家族性血液系统恶性肿瘤病例（包括几种白血病、淋巴瘤和骨髓综合征）和22例散发性急性白血病病例中的TP53基因。在1例诊断为急性淋巴细胞白血病的家族性病例中，我们报告了一个内含子替代559+1 G>A，它可能破坏剪接位点并影响正常蛋白质功能。国际癌症研究机构（IARC）数据库分类的大多数有害突变（Arg158His；Pro282Trp；Thr312Ser）在此处研究的所有急性淋巴细胞白血病病例中都有常见报道。在大多数患者中观察到两个变体rs1042522和rs1642785的共分离，这可能有利于连锁不平衡的存在。此处发现的最明确的TP53突变是在急性淋巴细胞白血病背景下鉴定的，而在先前的研究中只有3%的突变。两个反复出现的变体rs1042522和rs1642785的共分离应进一步得到证实。
