Non-V600 BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer
Non-V600 BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer
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DOI：
10.1200/jco.2016.71.4394
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发表时间：
2017-08-10
影响因子：
45.3
通讯作者：
Grothey, Axel
中科院分区：
文献类型：
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作者：
Jones, Jeremy C.;Renfro, Lindsay A.;Grothey, Axel
目的分子诊断检测已成为转移性结直肠癌（CRC）患者评估的一个组成部分。扩展的突变检测，如下一代测序（NGS），通常可以识别出临床或预后意义不明确的突变。一个这样的例子是BRAF突变发生以外的密码子600（（非V600）BRAF突变）。MethodsWe进行了这个多中心，回顾性队列研究，以表征临床，病理和生存的影响，非V600 BRAF突变转移性结直肠癌。我们汇集了非V600 BRAF突变的患者中确定从NGS数据库在三个大型分子遗传学参考laborators.ResultsA共9,643例转移性结直肠癌患者进行NGS测试。我们确定了208例非V600 BRAF突变患者，占所有检测患者的2.2%，占所有BRAF突变的22%。非V600 BRAF突变的癌症与V600 E BRAF突变的癌症相比（（V600 EBRAF））突变，发现在患者谁是显着年轻（分别为58岁和68岁），女性患者较少（分别为46%和65%），以及高级别肿瘤较少（分别为13%和64%）或右侧原发性肿瘤较少（分别为36%和81%）的患者。BRAF突变转移性结直肠癌患者的中位总生存期（非V600）明显长于EBRAF突变和野生型BRAF转移性结直肠癌患者（分别为60.7 v11.4 v43.0个月;P <0.001）。多因素分析显示，非V600 BRAF突变与总生存率的提高独立相关（hazard ratio，0.18; P <0.001）。(C)2017年美国临床肿瘤学会
PurposeMolecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 ((non-V600)BRAF mutations).MethodsWe conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of non-V600BRAF mutations in metastatic CRC. We pooled patients in whom non-V600BRAF mutations were identified from NGS databases at three large molecular genetics reference laboratories.ResultsA total of 9,643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with non-V600BRAF mutations, which occurred in 2.2% of all patients tested and accounted for 22% of all BRAF mutations identified. Cancers with non-V600BRAF mutations, compared with cancers with V600E BRAF ((V600EBRAF)) mutations, were found in patients who were significantly younger (58 v 68 years, respectively), fewer female patients (46% v 65%, respectively), and patients who had fewer high-grade tumors (13% v 64%, respectively) or right-sided primary tumors (36% v 81%, respectively). Median overall survival was significantly longer in patients with (non-V600)BRAF-mutant metastatic CRC compared with those with both (V600)EBRAF-mutant and wild-type BRAF metastatic CRC (60.7 v 11.4 v 43.0 months, respectively;P < .001). In multivariable analysis, non-V600BRAF mutation was independently associated with improved overall survival (hazard ratio, 0.18; P < .001).Conclusion(Non-V600)BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a clinically distinct subtype of CRC with an excellent prognosis. (C) 2017 by American Society of Clinical Oncology