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. 2013 Aug 7;105(15):1151-6.
doi: 10.1093/jnci/djt173. Epub 2013 Jul 22.

Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication

Paul Lochhead  1 , Aya Kuchiba, Yu Imamura, Xiaoyun Liao, Mai Yamauchi, Reiko Nishihara, Zhi Rong Qian, Teppei Morikawa, Jeanne Shen, Jeffrey A Meyerhardt, Charles S Fuchs, Shuji Ogino
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V体育官网入口 - Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication

Paul Lochhead et al. J Natl Cancer Inst. .

Abstract

BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAF-wild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF-wild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1. 60 (95% confidence interval [CI] =1. 12 to 2. 28; P = . 009), 0. 48 (95% CI = 0. 27 to 0. 87; P = . 02), and 0. 25 (95% CI = 0. 12 to 0. 52; P < . 001), respectively. No evidence existed for a differential prognostic role of BRAF mutation by MSI status (P(interaction) > VSports手机版. 50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification. .

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Figures

Figure 1.
Figure 1.
Kaplan–Meier survival plots for colorectal cancer according to combined MSI/BRAF subgroup. A) Colorectal cancer–specific survival. B) Overall survival. Multi-group log-rank P values demonstrate statistically significant deviation of any one of the survival curves from the null hypothesis. MSI = microsatellite instability; MSS = microsatellite stable.
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