Optimizing targeted therapeutic development: Analysis of a colorectal cancer patient population with the BRAFV600E mutation

克拉斯 医学 V600E型 结直肠癌 肿瘤科 内科学 一致性 直肠 癌症 微卫星不稳定性 原发性肿瘤 转移 突变 队列 阶段(地层学) 癌症研究 生物 遗传学 微卫星 等位基因 基因 古生物学
作者
Jeanne Tie,Peter Gibbs,Lara Lipton,Michael Christie,Robert N. Jorissen,Antony W. Burgess,Matthew Croxford,Ian T. Jones,Rachel Langland,Suzanne Kosmider,Daniel J. McKay,Gideon Bollag,K. B. Nolop,Oliver M. Sieber,Jayesh Desai
出处
期刊:International Journal of Cancer [Wiley]
卷期号:128 (9): 2075-2084 被引量:218
标识
DOI:10.1002/ijc.25555
摘要

BRAF(V600E) mutations are found in 10% of colorectal cancers (CRCs). The low frequency of this mutation therefore makes it a challenging target for drug development, unless subsets of patients with higher rates of BRAF(V600E) can be defined. Knowledge of the concordance between primary-metastasis pairs and the impact of BRAF(V600E) on outcome would also assist in optimal drug development. We selected primary CRCs from 525 patients (stages I-IV) evenly matched for age (<70 and ≥70), gender and tumor location (right, left and rectum), and 81 primary-metastasis pairs. BRAF(V600E), KRAS mutation and microsatellite instability (MSI) were determined and correlated with clinical features and patient outcomes. In multivariate analyses, increasing patient age (p = 0.04), female gender (p = 0.0005) and right-sided tumor location (p < 0.0001) were independently associated with BRAF(V600E). The prevalence of BRAF(V600E) was considerably higher in older (age > 70) females with KRAS wild-type right-sided colon cancers (50%) compared to the unselected cohort (10%). BRAF(V600E) was associated with inferior overall survival in metastatic CRC (HR = 2.02; 95% CI 1.26-3.26), particularly evident in patients treated with chemotherapy, and is independent of MSI status. BRAF status was concordant in all primary tumors and matched metastases (79 wild-type pairs and two mutant pairs). Clinicopathological and molecular features can identify CRC patients with a higher prevalence of BRAF(V600E). Patients with BRAF(V600E) wild-type primary tumor do not appear to acquire the mutation in their metastases, and BRAF(V600E) is associated with poorer outcomes in metastatic patients. Our findings are timely and will help inform the rational development of BRAF(V600E) inhibitors in CRC.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
粗心的小蜜蜂完成签到,获得积分10
2秒前
小小郭发布了新的文献求助30
4秒前
afree发布了新的文献求助30
4秒前
露亮发布了新的文献求助10
5秒前
hh完成签到 ,获得积分10
7秒前
浅陌完成签到,获得积分10
7秒前
Hello应助bwl采纳,获得10
7秒前
Aileenx关注了科研通微信公众号
7秒前
12发布了新的文献求助10
11秒前
能量球完成签到,获得积分10
11秒前
小朋友完成签到,获得积分10
11秒前
gugu完成签到,获得积分10
12秒前
14秒前
七慕凉应助JH采纳,获得10
15秒前
15秒前
17秒前
地表飞猪应助shimhjy采纳,获得20
17秒前
科研通AI5应助啊懂采纳,获得10
17秒前
刘明生发布了新的文献求助10
18秒前
20秒前
领导范儿应助afree采纳,获得30
21秒前
21秒前
22秒前
23秒前
23秒前
酥饼完成签到,获得积分10
24秒前
24秒前
yanzi发布了新的文献求助10
24秒前
25秒前
愉快的便当完成签到,获得积分10
26秒前
啊懂发布了新的文献求助10
26秒前
26秒前
王京发布了新的文献求助30
26秒前
憨憨发布了新的文献求助10
28秒前
陈陈陈完成签到 ,获得积分10
28秒前
牛牛发布了新的文献求助30
29秒前
29秒前
17852573662完成签到,获得积分10
29秒前
张卓发布了新的文献求助10
30秒前
30秒前
高分求助中
Technologies supporting mass customization of apparel: A pilot project 600
Introduction to Strong Mixing Conditions Volumes 1-3 500
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
Optical and electric properties of monocrystalline synthetic diamond irradiated by neutrons 320
共融服務學習指南 300
Essentials of Pharmacoeconomics: Health Economics and Outcomes Research 3rd Edition. by Karen Rascati 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3800648
求助须知:如何正确求助?哪些是违规求助? 3345863
关于积分的说明 10327533
捐赠科研通 3062411
什么是DOI,文献DOI怎么找? 1680986
邀请新用户注册赠送积分活动 807300
科研通“疑难数据库(出版商)”最低求助积分说明 763627