BRAF-V600E突变（mt）是转移性结直肠癌（mCRC）中强有力的负面预后和预测性生物标志物。非-V600E mt，被称为非典型BRAFmt（aBRAFmt），是罕见的，并且对其频率、共突变情况以及预后和预测作用知之甚少。本研究比较了三个北欧以人群为基础或真实世界队列中收集的mCRC患者的突变型群组之间的差异。研究了aBRAFmt的病理学。本研究包括1449例mCRC患者，其中51例（3%）是aBRAFmt，182例（13%）是BRAF-V600E mt，456例（31%）是RAS和BRAF野生型（wt），760例（52%）是RAS mt肿瘤。aBRAFmt在真实世界和基于人群的队列中分别占2%和4%。探测到了26种不同的aBRAFmt，其中11例（22%）属于2类（2/9个测试中的锯齿状腺癌），32例（64%）属于3类（25个样本中的15例锯齿状腺癌），4例（8%）为未分类。aBRAFmt患者以男性为主，主要为直肠原发灶，腹膜转移较少，在1例（2%）中发现缺乏错配修复，并且与BRAF-V600E mt相比，在转移切除后的生存率较好（89％的5年总生存率）。与RAS和BRAF wt以及RAS mt相比，aBRAFmt和BRAF-V600E mt的总体表现状态较差，接受了较少的治疗线。aBRAFmt的总生存期（中位数14.4个月）长于BRAF-V600E mt（11.2个月），但短于RAS和BRAF wt（30.5个月）以及RAS mt（23.4个月）。加用贝伐单抗趋向于改善aBRAFmt的总生存期。9例aBRAFmt患者接受了靶向药物西妥昔单抗/帕尼单抗治疗，但未见效果。aBRAFmt代表了与其他RAS/BRAF群组不同的亚组，只有一半患有锯齿状腺癌。aBRAFmt患者的肿瘤总体生存期略好于BRAF-V600E mt，但较RAS mt和RAS和BRAF wt差。aBRAFmt不应被视为转移切除的禁忌症。© 2023 The Authors. 由John Wiley & Sons Ltd代表UICC发表的《International Journal of Cancer》

BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.