Disruptive and Truncating TP53 Mutations Are Associated with African-Ancestry and Worse Prognosis in Brazilian Patients with Lung Adenocarcinoma.

IF 3.5 4区 医学 Q3 CELL BIOLOGY
Pathobiology Pub Date : 2023-01-01 Epub Date: 2023-04-08 DOI:10.1159/000530587
Rodrigo de Oliveira Cavagna, Icaro Alves Pinto, Flávia Escremim de Paula, Gustavo Noriz Berardinelli, Débora Sant'Anna, Iara Santana, Vinicius Duval da Silva, Eduardo Caetano Albino Da Silva, José Elias Miziara, Josiane Mourão Dias, Augusto Antoniazzi, Alexandre Jacinto, Pedro De Marchi, Miguel Angel Molina-Vila, Leticia Ferro Leal, Rui Manuel Reis
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引用次数: 1

Abstract

Introduction: TP53 is the most frequently mutated gene in lung tumors, but its prognostic role in admixed populations, such as Brazilians, remains unclear. In this study, we aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in non-small cell lung cancer (NSCLC) patients in Brazil.

Methods: We analyzed 446 NSCLC patients from Barretos Cancer Hospital. TP53 mutational status was evaluated through targeted next-generation sequencing (NGS) and the variants were biologically classified as disruptive/nondisruptive and as truncating/nontruncating. We also assessed genetic ancestry using 46 ancestry-informative markers. Analysis of lung adenocarcinomas from the cBioportal dataset was performed. We further examined associations of TP53 mutations with patients' clinicopathological features.

Results: TP53 mutations were detected in 64.3% (n = 287/446) of NSCLC cases, with a prevalence of 60.4% (n = 221/366) in lung adenocarcinomas. TP53 mutations were associated with brain metastasis at diagnosis, tobacco consumption, and higher African ancestry. Disruptive and truncating mutations were associated with a younger age at diagnosis. Additionally, cBioportal dataset revealed that TP53 mutations were associated with younger age and Black skin color. Patients harboring disruptive/truncating TP53 mutations had worse overall survival than nondisruptive/nontruncating and wild-type patients.

Conclusion: TP53 mutations are common in Brazilian lung adenocarcinomas, and their biological characterization as disruptive and truncating mutations is associated with African ancestry and shorter overall survival.

破坏性和截短性TP53突变与巴西肺腺癌患者的非洲祖先和更糟糕的预后有关。
引言:TP53是肺部肿瘤中最常见的突变基因,但其在混合人群(如巴西人)中的预后作用尚不清楚。在本研究中,我们旨在评估巴西非小细胞肺癌癌症(NSCLC)患者TP53突变的频率和临床病理影响。方法:我们分析了来自Barretos癌症医院的446例NSCLC患者。通过靶向下一代测序(NGS)评估TP53的突变状态,并将变体从生物学上分为破坏性/非破坏性和截断性/非截断性。我们还使用46个祖先信息标记评估了遗传祖先。对来自cBioportal数据集的肺腺癌进行分析。我们进一步研究了TP53突变与患者临床病理特征的关系。结果:在64.3%(n=287/446)的NSCLC病例中检测到TP53突变,在肺腺癌中的患病率为60.4%(n=221/366)。TP53突变与诊断时的脑转移、吸烟和较高的非洲血统有关。破坏性突变和截断性突变与诊断时年龄较小有关。此外,cBioportal数据集显示,TP53突变与年轻和黑人肤色有关。携带破坏性/截短型TP53突变的患者的总生存率低于非破坏性/非截短型和野生型患者。结论:TP53突变在巴西肺腺癌中很常见,其生物学特征为破坏性和截短性突变与非洲血统和较短的总生存期有关。
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来源期刊
Pathobiology
Pathobiology 医学-病理学
CiteScore
8.50
自引率
0.00%
发文量
47
审稿时长
>12 weeks
期刊介绍: ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.
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