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对BRAF突变的晚期胆道癌的比较基因组分析和临床结果

Tin-Yun Tang¹, Federico Nichetti^2,3, Ben Kaplan⁴

¹Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Clinical cancer research : an official journal of the American Association for Cancer Research

|September 29, 2023

概括

胆道癌 (BTC) 中的BRAF突变与第一线化疗的更差结果有关. 这些突变,特别是在肝内胆管癌 (iCCA) 中,也可能与其他可向突变相互排斥,影响治疗策略.

科学领域:

在瘤学瘤学.
遗传学遗传学是一个
癌症研究癌症研究

背景情况:

在胆道癌 (BTC) 中,BRAF突变不常见,但由于新兴的向疗法,它们很重要.
了解BTC中BRAF突变的临床和基因组影响对于优化治疗策略至关重要.

研究的目的:

为了研究BRAF突变先进BTC治疗第一线化疗的临床结果.
探索BTC的肝脏内胆管癌 (iCCA) 亚组中的BRAF类I,II和III突变的基因组景观.

主要方法:

分析了两个队列:iCCA中BRAF突变格局的基因组队列和高级BTC中生存结果的临床队列.
在接受一线化疗的BRAF突变BTC患者中,评估无进展生存 (PFS) 和整体生存 (OS).

主要成果:

在总体BTC临床队列中,与BRAF野生型 (WT) 相比,BRAF突变 (I,II和III类) 与PFS和OS的显著缩短有关.
在iCCA亚组中,I类BRAF突变与FGFR2,IDH1/2,ERBB2和KRAS突变相互排斥.
在iCCA中,II+III类BRAF突变与FGFR2和KRAS突变显示出相互排他性.

结论:

在BTC中,所有类型的BRAF突变都与更差的预后有关.
在iCCA亚组中,BRAF突变在约5%的患者中被发现.
在iCCA中,BRAF突变与其他可向突变的相互排他性表明对组合疗法的潜在影响.

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