國家衛生研究院 NHRI:Item 3990099045/9308
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    题名: Mutation spectra of common cancer-associated genes in different phenotypes of colorectal carcinoma without distant metastasis
    作者: Chang, SC;Lin, PC;Lin, JK;Lin, CH;Yang, SH;Liang, WY;Chen, WS;Jiang, JK
    贡献者: Institute of Molecular and Genomic Medicine
    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 - betaR (9.6 %) mutation frequencies were significantly higher in proximal colon cancer. The high MSI (35.6 %) and BRAF (20.3 %), TGF - betaR (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.
    日期: 2016-03
    關聯: Annals of Surgical Oncology. 2016 Mar;23(3):849-855.
    Link to: http://dx.doi.org/10.1245/s10434-015-4899-z
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1068-9265&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000371334600022
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84957846494
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