Mutation Spectra of Common Cancer-Associated Genes in Different Phenotypes of Colorectal Carcinoma Without Distant Metastasis

Shih Ching Chang, Pei Ching Lin, Jen Kou Lin, Chien Hsing Lin, Shung Haur Yang, Wen Yi Liang, Wei Shone Chen, Jeng Kai Jiang*

*此作品的通信作者

研究成果: Article同行評審

24 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)849-855
頁數7
期刊Annals of Surgical Oncology
23
發行號3
DOIs
出版狀態Published - 1 3月 2016

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