Class1/2/3 BRAF基因突变结直肠癌的临床和基因组学区别及不同的预后。
The clinical and genomic distinctions of Class1/2/3 BRAF-mutant colorectal cancer and differential prognoses.
发表日期:2023 Jan 25
作者:
Yungchang Chen, Hao Sun, Yanhong Deng, Yutong Ma, He Huang, Yang Liu, Yaru Zhang, Hongyu Zhang, Sheng Ye, Mingyan E, Hongqiang Guo, Mengmeng Wu, Chunman Wu, Xingxiang Pu, Xinggui Chen, Chaoyong Liang, Qiuxiang Ou, Huawei Weng, Xue Wu, Yang Shao, Anxin Gu, Tongyu Lin
来源:
Biomarker Research
摘要:
BRAF突变是结肠癌的致癌驱动因素,常见的变异类型为V600(Class1),导致无关RAS激活单体。BRAF非V600突变体可以进一步分类为RAS独立活性二聚体(Class2)和RAS依赖性受损激酶(Class3)。我们对328个未接受治疗的结肠癌患者进行回顾性突变分析,使用捕获基因杂交下一代测序技术,针对400多个与癌症相关的基因检测到BRAF突变。我们研究了携带Class1/2/3 BRAF突变的患者的临床和基因学差异,发现携带Class1 BRAF突变的肿瘤显示出更独特的基因组特征。此外,使用cBioPortal的外部数据集,我们证明携带Class3 BRAF突变的患者比其他两个亚组具有最佳生存结局。这些发现有助于通过鉴别BRAF突变亚型来促进抗BRAF策略的发展。 © 2023.作者(S)。
BRAF mutations are the oncogenic drivers in colorectal cancer and V600 mutations (Class1), which lead to RAS-independent active monomers, are the most common mutation types. BRAF non-V600 mutants can be further classified as RAS-independent active dimers (Class2) and RAS-dependent impaired kinase (Class3). We retrospectively reviewed the mutational profiles of 328 treatment-naïve colorectal tumors with BRAF mutations detected using capture-based hybrid next-generation sequencing targeting 400 + cancer-related genes. The clinical and genetic distinctions of patients harboring Class1/2/3 BRAF mutations were investigated, which revealed that tumors with Class1 BRAF mutations showed more unique genomic profiles than those with Class2/3 mutations. Also, by using an external dataset from cBioPortal, we demonstrated that patients with Class3 BRAF mutations had the best survival outcomes compared to the other two subgroups. These findings promoted the development of anti-BRAF strategies by distinguishing BRAF mutant subgroups.© 2023. The Author(s).