Souad Kartti, El Mehdi Bouricha, Oumaima Zarrik, Youssef Aghlallou, Chaimaa Mounjid, Rachid ELJaoudi, Lahcen Belyamani, Azeddine Ibrahimi, Basma El Khannoussi
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引用次数: 0
摘要
基于下一代测序的临床研究新基因面板的日益商业化,大大提高了我们对乳腺癌遗传学的理解,并导致了新的突变变体的发现。该研究包括16名未选择的摩洛哥乳腺癌患者,使用Illumina Miseq进行多基因面板(HEVA筛选面板)测试,然后进行Sanger测序以验证最相关的突变。突变分析显示存在13个突变(11个单核苷酸多态性[SNPs]和2个indel),鉴定出的11个snp中有6个被预测为致病性。6个致病性突变之一是BRCA2基因HD-OB结构域的杂合SNP C . 7874g >C,导致该蛋白密码子2625处精氨酸向苏氨酸转变。本研究描述了第一例携带该致病变异的乳腺癌患者,并利用分子对接和分子动力学模拟分析了其功能影响。需要进一步的实验研究来证实其致病性并证实其与乳腺癌的关联。
Targeted Gene Panel Sequencing Unveiled New Pathogenic Mutations in Patients With Breast Cancer.
The increasing commercialization of new gene panels based on next-generation sequencing for clinical research has significantly improved our understanding of breast cancer genetics and has led to the discovery of new mutation variants. The study included 16 unselected Moroccan breast cancer patients tested with multi-gene panel (HEVA screen panel) using Illumina Miseq, followed by Sanger sequencing to validate the most relevant mutation. Mutational analysis revealed the presence of 13 mutations (11 single-nucleotide polymorphisms [SNPs] and 2 indels), and 6 of 11 identified SNPs were predicted as pathogenic. One of the 6 pathogenic mutations was c.7874G>C, a heterozygous SNP in HD-OB domain of BRCA2 gene, which led to the arginine to threonine change at codon 2625 of the protein. This work describes the first case of a patient with breast cancer harboring this pathogenic variant and analyzes its functional impact using molecular docking and molecular dynamics simulation. Further experimental investigations are needed to validate its pathogenicity and to verify its association with breast cancer.
期刊介绍:
Bioinformatics and Biology Insights is an open access, peer-reviewed journal that considers articles on bioinformatics methods and their applications which must pertain to biological insights. All papers should be easily amenable to biologists and as such help bridge the gap between theories and applications.