BRAF 突变与 IDH1/2 突变同时存在于伴 BRAF 突变的成人脑胶质瘤患者中比在无 BRAF 突变但具有生存优势的患者中更常见。

BRAF more frequently co-occurs with IDH1/2 mutations in adult patients with gliomas than in patients harboring BRAF but without a survival advantage.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, No.277 Yanta West Road, Xi'an, 710061, Shaanxi, China.

出版信息

BMC Neurol. 2021 May 12;21(1):195. doi: 10.1186/s12883-021-02224-6.

DOI:10.1186/s12883-021-02224-6

PMID:33980169

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8114535/

Abstract

BACKGROUND

The effects of BRAF and BRAF on the outcomes and the molecular characteristics of adult glioma patients are unknown and need to be explored, although BRAF has been extensively studied in pediatric glioma.

METHODS

Co-occurring mutations and copy number alterations of associated genes in the MAPK and p53 pathways were investigated using data from The Cancer Genome Atlas (TCGA) public database retrieved by cBioPortal. The prognosis of available adult glioma cohorts with BRAF and BRAF mutations were also investigated.

RESULTS

Ninety patients with BRAF or BRAF were enrolled in this study, and data from 52 nonredundant patients were investigated. Glioblastoma multiform was the most common cancer type, with BRAF and BRAF. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAF than in BRAF, and TP53 was an independent risk factor (56.00% vs. 7.41%). Both BRAF and BRAF frequently overlapped with CDKN2A/2B homozygous deletions (HDs), but there was no significant difference. Survival analysis showed no difference between the BRAF and BRAF cohorts, even after excluding the survival benefit of IDH1/2 mutations and considering the BRAF mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of patients with BRAF & IDH1/2 with mutations in the G-loop groups was the shortest.

CONCLUSIONS

BRAF exhibited a stronger association with IDH1/2 mutations than BRAF, but no survival advantage was found.

摘要

背景

BRAF 和 BRAF 对成人胶质瘤患者的结局和分子特征的影响尚不清楚，需要进一步探索，尽管 BRAF 在儿科胶质瘤中已得到广泛研究。

方法

使用 cBioPortal 从癌症基因组图谱（TCGA）公共数据库中检索的数据，研究 MAPK 和 p53 通路中相关基因的共发生突变和拷贝数改变。还研究了 BRAF 和 BRAF 突变的可用成人胶质瘤队列的预后。

结果

本研究共纳入 90 例 BRAF 或 BRAF 患者，其中 52 例非冗余患者的数据进行了研究。多形性胶质母细胞瘤是最常见的癌症类型，BRAF 和 BRAF 突变分别占 67.78%和 32.22%。与 BRAF 相比，BRAF 中 TP53（56.00%比 7.41%）、IDH1/2（36.00%比 3.70%）和 ATRX（32.00%比 7.41%）的突变更为常见，且 TP53 是独立的危险因素（56.00%比 7.41%）。BRAF 和 BRAF 均常与 CDKN2A/2B 纯合缺失（HD）重叠，但无显著性差异。生存分析显示，即使排除 IDH1/2 突变的生存获益并考虑甘氨酸丰富环（G 环）和激活片段中的 BRAF 突变，BRAF 和 BRAF 队列之间也无差异。BRAF&IDH1/2 突变且 G 环组突变的患者估计平均生存时间最短。