Related Experiment Video
Updated: Jun 19, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Genomic Alterations and Clinical Characterization in Chinese Patients with Metastatic Colorectal Cancer
Xu-Hui Zhang1, Jie-Qiong Zhou2, Qing Wei3
1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 100142 Beijing, China.
Background:
Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as RAS, BRAF, and microsatellite instability (MSI). Novel genomic changes, including ERBB2 amplifications, mutations, and gene fusions, are now recognized as potential targets for precision therapy. This study aims to explore the genomic landscape of a Chinese cohort with mCRC to identify potentially targetable genetic alterations for personalized treatment strategies.
Methods:
A total of 500 mCRC patients in China were enrolled, based on which genomic profiling was performed using capture-based targeted sequencing across a panel of 520 genes on tumor tissues to identify prevalent genomic alterations. The mutations were analyzed by optimized proprietary algorithms. MSI and mismatch repair deficiency status were analyzed using the read-count-distribution approach. Besides, the overall survival (OS) related to these molecular changes was estimated.
Results:
The cohort's genomic profiling revealed TP53 mutations in 78%, APC in 60%, and KRAS in 47% of the patients. MSI-High status was confirmed in 5.8% of cases via a next-generation sequencing (NGS)-based algorithm. ERBB2/HER2 amplifications were found in 12% (60/500) of patients, with potential therapeutic implications for those without concurrent KRAS mutations. A subset of patients (1.2%; 6/500) showed fusions and DNA damage response (DDR) gene mutations (except TP53) that could be targeted therapeutically. The KRAS (G12C) variant was detected in 14 patients (2.8%), and 61 (12.2%) had a BRAF V600E mutation. Notably, survival analysis showed no significant differences in OS between KRAS mutant loci and NRAS mutations (p = 0.436). However, BRAF V600E mutations were associated with a poorer prognosis than BRAF wild-type and non-V600E mutations (16.3 months vs. 29.5 and 31.1 months, respectively; p < 0.001).
Conclusions:
This study validates the feasibility of using NGS to detect prognostic and therapeutically actionable genetic variants in Chinese mCRC patients, contributing to understanding the genomic variation within this population and highlighting the potential for personalized medicine in managing mCRC.
Insights
Genomic profiling of Chinese metastatic colorectal cancer (mCRC) patients revealed frequent TP53 and APC mutations, alongside actionable ERBB2 amplifications and BRAF V600E mutations, guiding personalized therapy strategies.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Metastatic colorectal cancer (mCRC) exhibits diverse genomic alterations beyond established markers.
- Emerging targets like ERBB2 amplifications, mutations, and fusions offer new therapeutic avenues.
- Understanding the genomic landscape in specific populations is crucial for personalized treatment.
Purpose of the Study:
- To comprehensively analyze the genomic profile of a Chinese mCRC cohort.
- To identify prevalent and potentially targetable genetic alterations.
- To correlate molecular findings with overall survival (OS) for prognostic insights.
Main Methods:
- Targeted next-generation sequencing (NGS) of 520 genes on tumor tissues from 500 mCRC patients.
- Analysis of mutations, microsatellite instability (MSI), and mismatch repair deficiency.
- Estimation of overall survival (OS) in relation to identified molecular alterations.
Main Results:
- High frequencies of TP53 (78%), APC (60%), and KRAS (47%) mutations were observed.
- ERBB2/HER2 amplifications occurred in 12% of patients, with therapeutic potential.
- BRAF V600E mutations (12.2%) were linked to poorer prognosis, while KRAS mutations did not significantly impact OS.
Conclusions:
- NGS is effective for detecting prognostic and actionable variants in Chinese mCRC patients.
- This study enhances understanding of genomic variations in this population.
- Findings support the potential of personalized medicine for mCRC management.
More Related Videos
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
