Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland,
Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Pathobiology. 2023;90(3):166-175. doi: 10.1159/000526117. Epub 2022 Oct 6.
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.
We report the molecular profile of 512 Swiss CRC patients analyzed by targeted next-generation sequencing as part of routine diagnostics at our institute.
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.
结直肠癌（CRC）是男性和女性中最常见的癌症之一。在晚期，患者根据 RAS 状态进行治疗。最近的研究表明，除了 KRAS 和 NRAS 外，其他基因的改变，如 PIK3CA 或 TP53，也将被考虑用于治疗。因此，了解常规诊断 CRC 的突变景观非常重要。
我们报告了 512 例瑞士 CRC 患者的分子谱，这些患者是作为我们研究所常规诊断的一部分通过靶向下一代测序进行分析的。
在 462 例（90%）CRC 患者中发现了致病性和可能致病性的变异。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。其余的致病性改变发生在 ATM（n=1）、MAP2K1（n=1）和 IDH2（n=1）基因中。
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流行率。此外，我们的研究是瑞士首次对 CRC 的分子景观进行的此类大型研究。
