Mutation Spectra of Common Cancer-Associated Genes in Different Phenotypes of Colorectal Carcinoma Without Distant Metastasis
Abstract
Background Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. This study aimed to describe the mutation frequency of 12 genes in different CRC phenotypes. Methods Patients who underwent surgery at the Taipei Veterans General Hospital during 2000-2010 for CRC (n = 1249) were enrolled. The endpoint was overall survival. The prognostic value was determined with the log-rank test and Cox regression analysis. Results We found 1836 mutations of 12 genes in 997 (79.8%) tumors. Mutations were most frequently in KRAS (485, 38.8%), TP53 (373, 29.9%), APC (363, 29.0%), and PIK3CA (179, 14.3%); 137 (11.0%) cancers had high microsatellite instability (MSI). Women had significantly higher high MSI (14.3%) and BRAF mutation (6.3%) frequencies. The abnormal MSI (21.7%) and KRAS (44.6%), BRAF (8.6%), PIK3CA (19.4%), AKT1 (2.2%), and TGF - βR (9.6%) mutation frequencies were significantly higher in proximal colon cancer. The high MSI (35.6%) and BRAF (20.3%), TGF - βR (18.6%), PTEN (5.1%), and AKT1 (3.4%) mutation frequencies were significantly higher in 59 (4.7%) poorly differentiated tumors. The high MSI (21.3%) and KRAS (51.9%), BRAF (8.3%), PIK3CA (25.0%), AKT1 (4.6%), and SMAD4 (8.3%) mutation frequencies were significantly higher in 108 mucinous tumors. TNM stage, lymphovascular invasion, and mucinous histology were significantly associated with patient outcomes in univariate and multivariate analyses. Only NRAS mutation (hazard ratio 1.59, 95% confidence interval 1.06-2.38) affected patient survival. Conclusions Mutational spectra differ significantly between CRC subtypes, implying diverse carcinogenetic pathways. The NRAS mutation is important, despite its low frequency.
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Mucinous tumor tissue has been linked to KRAS mutational burden.
“which has also been linked to KRAS mutational burden50,56.”
From Self-supervised learning reveals clinically relevant histomorphological patterns for therapeutic strategies in colon cancer (2025) · cites this paper as [56]
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- Authors
- Chang, S.-C., Lin, P.-C., Lin, J.-K., Lin, C.-H., Yang, S.-H., Liang, W.-Y., Chen, W.-S., & Jiang, J.-K.
- Affiliations
- Taipei Veterans General Hospital (TW)
- Taipei Municipal YangMing Hospital (TW)
- National Health Research Institutes (TW)
- Corresponding author
- Jiang, Jeng-Kai
- Venue
- Annals of Surgical Oncology
- Published
- 2015-10-15
- Volume
- 23
- Issue
- 3
- Pages
- 849-855
- ISSN
- 1068-9265 (ISSN-L)
- 1534-4681
- OpenAlex
- W2187184853
- Cited by
- 31
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2021: 4 · 2020: 1 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 4
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Annals of Surgical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Taipei Veterans General Hospital
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer, somatic mutations, KRAS, TP53, APC, PIK3CA, microsatellite instability, BRAF, NRAS, TGF-beta receptor, PTEN, AKT1, SMAD4, mucinous carcinoma, right-sided colon cancer, poorly differentiated tumors, tumor subtypes, prognostic value, overall survival
- MeSH terms
- Adult, Aged, Aged, 80 and over, Adenocarcinoma, Mucinous, Female, Follow-Up Studies, Humans, Male, Middle Aged, Mutation, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Neoplasm Staging, Phenotype, Prognosis, Proto-Oncogene Proteins, Biomarkers, Tumor, Colorectal Neoplasms, Survival Rate, Microsatellite Instability
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