Prevalence of Molecular Alterations in a Swiss Cohort of 512 Colorectal Carcinoma Patients by Targeted Next-Generation Sequencing Analysis in Routine Diagnostics.

IF 3.5 4区医学 Q3 CELL BIOLOGY

Pathobiology Pub Date : 2023-01-01 DOI:10.1159/000526117

Simon Haefliger, Katharina Marston, Ilaria Alborelli, Edouard-Jean Stauffer, Mathias Gugger, Philip M Jermann, Sylvia Hoeller, Luigi Tornillo, Luigi M Terracciano, Michel Bihl, Matthias S Matter

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引用次数: 1

Abstract

Introduction: Colorectal carcinoma (CRC) is among the most common carcinomas in women and men. In the advanced stage, patients are treated based on the RAS status. Recent studies indicate that in the future, in addition to KRAS and NRAS, alterations in other genes, such as PIK3CA or TP53, will be considered for therapy. Therefore, it is important to know the mutational landscape of routinely diagnosed CRC.

Method: We report the molecular profile of 512 Swiss CRC patients analyzed by targeted next-generation sequencing as part of routine diagnostics at our institute.

Results: Pathogenic and likely pathogenic variants were found in 462 (90%) CRC patients. Variants were detected in TP53 (54.3%), KRAS (48.2%), PIK3CA (15.6%), BRAF (13.5%), SMAD4 (10.5%), FBXW7 (7.8%), NRAS (3.5%), PTEN (2.7%), ERBB2 (1.6%), AKT1 (1.5%), and CTNNB1 (0.9%). The remaining pathogenic alterations were found in the genes ATM(n= 1), MAP2K1(n= 1), and IDH2(n= 1).

Discussion/conclusions: Our analysis revealed the prevalence of potential predictive markers in a large cohort of CRC patients obtained during routine diagnostic analysis. Furthermore, our study is the first of this size to uncover the molecular landscape of CRC in Switzerland.

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通过靶向新一代测序分析常规诊断中512名瑞士结直肠癌患者分子改变的患病率

结直肠癌(CRC)是男性和女性中最常见的癌症之一。在晚期，根据RAS状态对患者进行治疗。最近的研究表明，在未来，除了KRAS和NRAS，其他基因的改变，如PIK3CA或TP53，将被考虑用于治疗。因此，了解常规诊断的结直肠癌的突变情况非常重要。方法:我们报告了512名瑞士CRC患者的分子谱，通过靶向下一代测序作为我们研究所常规诊断的一部分进行分析。结果:在462例(90%)结直肠癌患者中发现致病性和可能致病性变异。在TP53(54.3%)、KRAS(48.2%)、PIK3CA(15.6%)、BRAF(13.5%)、SMAD4(10.5%)、FBXW7(7.8%)、NRAS(3.5%)、PTEN(2.7%)、ERBB2(1.6%)、AKT1(1.5%)和CTNNB1(0.9%)中检测到变异。其余的致病改变在ATM(n= 1)、MAP2K1(n= 1)和IDH2(n= 1)基因中发现。讨论/结论:我们的分析揭示了在常规诊断分析中获得的大量CRC患者中潜在预测标志物的患病率。此外，我们的研究是第一个揭示瑞士CRC分子景观的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathobiology 医学-病理学

CiteScore

8.50

自引率

0.00%

发文量

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.