软组织肉瘤患者的BRAF突变和同时发生的变化
Hiroshi Kobayashi1, Liuzhe Zhang1, Koichi Okajima1
1Department of Orthopaedic Surgery, The University of Tokyo, Tokyo, Japan.
Genes, chromosomes & cancer
|June 9, 2023
概括
包括突变和融合在内的BRAF变异发生在1.2%的高级软组织肉瘤 (STS) 患者中. 了解这些BRAF变异和并发的基因变化对于开发有针对性的治疗策略至关重要.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 在软组织肉瘤 (STS) 中,很少报告BRAF变异 (V600E突变,非V600E突变,融合).
- 有限的病例系列强调了需要进行更大规模的研究,以确定STS中BRAF变化的频率和临床相关性.
研究的目的:
- 评估BRAF突变和融合在高级STS患者的大队伍中的频率.
- 调查与STS.中BRAF变异相关的同时发生的基因变异.
- 为BRAF改变的STS提供潜在的治疗策略.
主要方法:
- 综合基因组剖析数据的回顾性分析来自日本1964年高级STS患者 (2019年6月 - 2023年3月).
- 识别和量化 BRAF V600E 突变,非 V600E 突变和 BRAF 融合.
- 对复发性并发基因变异的分析,包括CDKN2A,TERT促进体,TP53和MAPK通路基因 (NF1,GNAQ,GNA11).
主要成果:
- 在1.2% (24/1964) 的晚期STS患者中检测到BRAF变化.
- BRAF V600E突变发生在0.6% (11/1964),非V600E突变发生在4.6% (9/1964),BRAF融合发生在0.2% (4/1964).
- CDKN2A变异是最常见的并发变异 (45.8%),其次是TERT促进子突变 (29.2%). 在非V600E组中,TP53变异和MAPK激活基因更频繁.
结论:
- BRAF变化代表了先进的STS的可向子集,在1.2%的患者中发生.
- 像CDKN2A,TERT促进体,TP53和MAPK通路基因等同时发生的改变,为BRAF改变的STS的分子格局提供了洞察力.
- 这些发现支持针对BRAF改变的高级STS患者的临床表征和向治疗的开发.
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