Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations

IF 4.8 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Jing Hu , Xinyi Chen , Feifei Sun , Lili Liu , Long Liu , Zimeng Yang , Hanwen Zhang , Zeyuan Yu , Ru Zhao , Yueyao Wang , Hui Liu , Xiaorong Yang , Fusheng Sun , Bo Han
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引用次数: 0

Abstract

While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAFK601E and BRAFL597R exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

在中国前列腺导管内癌中发现复发性 BRAF 非 V600 基因突变
虽然 BRAF 改变已被确定为各种实体恶性肿瘤的驱动因素,但前列腺癌(PCa)中 BRAF 改变的特征尚未得到彻底研究。通过生物信息学分析,我们首次发现 BRAF 基因改变与晚期 PCa 有关,并且在多个队列中与 ERG 基因改变表现出相互排斥的模式。最令人感兴趣的是,在 21 例表现为 IDC-P 形态的 PCa 患者中,有 3 例(14.3%)发现了复发性非 V600 BRAF 突变。此外,BRAFK601E 和 BRAFL597R 的实验性过表达表现出体外 MAPK 信号转导增强的致癌表型,MEK 抑制剂可将其作为靶点。比较中西方血统的 IDC-P 中 BRAF 基因改变的发生率发现,中国人的发生率更高。BRAF突变可能代表了IDC-P亚群中的重要基因改变,凸显了MAPK信号通路在该亚型PCa中的作用。据目前所知,这是首次在IDC-P中发现非V600 BRAF突变,这可能在一定程度上解释了IDC-P的侵袭性表型,也为携带此类突变的IDC-P PCa患者带来了更多的治疗选择。
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来源期刊
Neoplasia
Neoplasia 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
82
审稿时长
26 days
期刊介绍: Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.
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