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

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

doi:10.1159/000526117

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

Pathobiology. 2023;90(3):166-175. doi: 10.1159/000526117. Epub 2022 Oct 6.

Affiliations

¹ Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland, s.haefliger@hotmail.com.
² Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
³ Institute of Pathology, Promed Laboratoire Médical SA, Fribourg, Switzerland.

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.

Keywords: BRAF; Biomarkers; Cetuximab; Chromosome instability; Colon cancer; EGFR; KRAS; Microsatellite instability; Panitumumab.

MeSH terms

Class I Phosphatidylinositol 3-Kinases / genetics
Colorectal Neoplasms* / diagnosis
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / pathology
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Mutation
Prevalence
Proto-Oncogene Proteins p21(ras)* / genetics
Switzerland / epidemiology

Substances

Proto-Oncogene Proteins p21(ras)
Class I Phosphatidylinositol 3-Kinases

Grants and funding

Swiss Cancer Research Foundation Grant KFS-4168-02-2017 and Swiss National Science Foundation (SNSF; Grant No. 320030_189275) to Matthias S. Matter. The sponsor of the study did not have any role in the study design or collection, analysis, and interpretation of data.