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ERBB2 Mutations as Potential Predictors for Recurrence in Colorectal Serrated Polyps by Targeted Next-Generation
Qi-Wen Wang1, Xin-Yuan Wang1, Qing-Wei Zhang1
1Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Individuals with serrated polyps (SPs) and ERBB2 mutations face higher risks of subsequent colorectal neoplasms. ERBB2 mutations may serve as predictive markers for high-risk SPs, potentially revealing mechanisms in the serrated pathway to colorectal cancer.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- Follow-up guidelines for serrated polyps (SPs) lack robust evidence, particularly regarding genomic factors influencing recurrence risk.
- The genomic mechanisms underlying SP recurrence risk remain largely unknown, necessitating further investigation.
Purpose of the Study:
- To investigate the genomic differences between polyp-relapsed SPs (PRSPs) and polyp-free SPs (PFSPs) using targeted next-generation sequencing (NGS).
- To identify potential genomic markers associated with SP recurrence risk and validate findings in a multicenter cohort.
Main Methods:
- Targeted NGS of 71 colorectal cancer-associated genes was performed on 96 SP samples, comparing PRSPs and PFSPs.
- A multicenter validation cohort of 321 SPs was established from 2016 to 2019 to confirm initial findings.
Main Results:
- Ninety-four percent of SP samples (90/96) harbored at least one mutation. BRAF, KRAS, and APC were the most frequently mutated genes.
- ERBB2 mutations (R678Q, V842I) were significantly associated with higher polyp recurrence risk (HR=4.9) and shorter polyp-free intervals (15 vs. 26 months).
- Validation in a multicenter cohort confirmed that ERBB2-mutated SPs had increased risks of polyp recurrence (HR=3.7) and advanced neoplastic lesion recurrence (HR=10.0).
Conclusions:
- Individuals with ERBB2-mutated SPs are at a significantly higher risk of subsequent colorectal neoplasms.
- ERBB2 mutations may serve as predictive biomarkers for identifying high-risk SPs and understanding their role in colorectal cancer development via the serrated pathway.
