Cytogenetic abnormalities and TP53 and RAS gene profiles of childhood acute lymphoblastic leukemia in Morocco

IF 1.3 4区 医学 Q3 PEDIATRICS
Hanaa Skhoun , Meriem El Fessikh , Mohamed El Alaoui Al Abdallaoui , Mohammed Khattab , Aziza Belkhayat , Zahra Takki Chebihi , Amale Hassani , Rachid Abilkassem , Aomar Agadr , Nadia Dakka , Jamila El Baghdadi
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引用次数: 0

Abstract

Background

Recurrent genetic abnormalities affecting pivotal signaling pathways are the hallmark of childhood acute lymphoblastic leukemia (ALL). The identification of these aberrations remains clinically important. Therefore, we sought to determine the cytogenetic profile and the mutational status of TP53 and RAS genes among Moroccan childhood cases of ALL.

Methods

In total, 35 patients with childhood ALL were enrolled in the study. The diagnosis and treatment were established in the Pediatric Hematology and Oncology Center at the Children's Hospital of Rabat. Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Blood samples were screened for TP53 and RAS mutations using Sanger sequencing.

Results

Of the 35 cases, 30 were B-lineage ALL (85.7 %). Moreover, a male predominance was observed. Cytogenetic analysis revealed chromosomal anomalies in 27 cases (77.1 %). The most frequent aberrations were high hyperdiploidy and BCR/ABL rearrangement. Interestingly, we found the rare t(15;16) and the t(8;14), which are uncommon translocations in pediatric B-ALL. The mutational analysis revealed Pro72Arg (rs1042522:C > G) and Arg213Arg (rs1800372:A > G) in TP53. In correlation with cytogenetic data, rs1042522:C > G showed a significant association with the occurrence of chromosomal translocations (p = 0.04). However, no variant was detected in NRAS and KRAS genes.

Conclusion

Our findings emphasize the significance of detecting chromosomal abnormalities as relevant prognostic markers. We also suggest a low occurrence of genetic variants among Moroccan children with ALL.

摩洛哥儿童急性淋巴细胞白血病的细胞遗传学异常及 TP53 和 RAS 基因图谱。
背景:影响关键信号通路的复发性遗传异常是儿童急性淋巴细胞白血病(ALL)的特征。识别这些畸变仍具有重要的临床意义。因此,我们试图确定摩洛哥儿童 ALL 病例的细胞遗传学特征以及 TP53 和 RAS 基因的突变状态:本研究共纳入 35 例儿童 ALL 患者。诊断和治疗均在拉巴特儿童医院小儿血液与肿瘤中心进行。研究采用染色体带状分析和荧光原位杂交技术检测基因畸变。利用桑格测序法对血液样本进行 TP53 和 RAS 基因突变筛查:35例病例中,30例为B系ALL(85.7%)。此外,男性患者占多数。细胞遗传学分析显示,27例(77.1%)患者染色体异常。最常见的畸变是高度二倍体和BCR/ABL重排。有趣的是,我们发现了罕见的t(15;16)和t(8;14),这在小儿B-ALL中是不常见的易位。突变分析显示,TP53中存在Pro72Arg(rs1042522:C > G)和Arg213Arg(rs1800372:A > G)。与细胞遗传学数据相关,rs1042522:C > G 与染色体易位的发生有显著关联(p = 0.04)。然而,在 NRAS 和 KRAS 基因中未检测到变异:我们的研究结果强调了检测染色体异常作为相关预后标记的重要性。我们还发现,在摩洛哥的 ALL 儿童中,基因变异的发生率较低。
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来源期刊
Archives De Pediatrie
Archives De Pediatrie 医学-小儿科
CiteScore
2.80
自引率
5.60%
发文量
106
审稿时长
24.1 weeks
期刊介绍: Archives de Pédiatrie publishes in English original Research papers, Review articles, Short communications, Practice guidelines, Editorials and Letters in all fields relevant to pediatrics. Eight issues of Archives de Pédiatrie are released annually, as well as supplementary and special editions to complete these regular issues. All manuscripts submitted to the journal are subjected to peer review by international experts, and must: Be written in excellent English, clear and easy to understand, precise and concise; Bring new, interesting, valid information - and improve clinical care or guide future research; Be solely the work of the author(s) stated; Not have been previously published elsewhere and not be under consideration by another journal; Be in accordance with the journal''s Guide for Authors'' instructions: manuscripts that fail to comply with these rules may be returned to the authors without being reviewed. Under no circumstances does the journal guarantee publication before the editorial board makes its final decision. Archives de Pédiatrie is the official publication of the French Society of Pediatrics.
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