NRG1 Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in KRAS Wild-Type Pancreatic Ductal Adenocarcinoma
NRG1 Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in KRAS Wild-Type Pancreatic Ductal Adenocarcinoma
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DOI：
10.1158/1078-0432.ccr-19-0191
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发表时间：
2019-08-01
影响因子：
11.5
通讯作者：
Renouf, Daniel J.
中科院分区：
文献类型：
--
作者：
Jones, Martin R.;Williamson, Laura M.;Renouf, Daniel J.
目的：涉及神经调节蛋白1（NRG 1）的基因融合已在多种癌症类型中发现，并具有潜在的治疗意义。虽然不同的结果已在其他癌症类型的报道，HER家族激酶抑制剂阿法替尼在治疗NRG 1融合阳性胰腺导管adenocarcinoma的疗效尚未完全understood.Experimental Design：47例胰腺导管腺癌患者接受了全面的全基因组和转录组测序和分析。两名患者的基因融合，涉及NRG 1接受阿法替尼治疗，治疗前和治疗后的PET/CT imaging.Results的反应测量：三个47（6%）晚期胰腺导管腺癌患者被确定为KRAS野生型全基因组测序。所有KRAS野生型肿瘤均为涉及ERBB 3配体NRG 1的基因融合阳性。两个与NRG 1融合阳性肿瘤的3例患者与阿法替尼治疗，并表现出显着的和快速的反应，而在therapy.Conclusions：这项工作增加了越来越多的证据表明，NRG 1基因融合是经常性的，在胰腺癌的治疗可操作的基因组事件。基于本文描述的临床结局，携带NRG 1基因融合的KRAS野生型肿瘤患者可能从阿法替尼治疗中获益。
Purpose: Gene fusions involving neuregulin 1 (NRG1) have been noted in multiple cancer types and have potential therapeutic implications. Although varying results have been reported in other cancer types, the efficacy of the HER-family kinase inhibitor afatinib in the treatment of NRG1 fusionpositive pancreatic ductal adenocarcinoma is not fully understood.Experimental Design: Forty-seven patients with pancreatic ductal adenocarcinoma received comprehensive wholegenome and transcriptome sequencing and analysis. Two patients with gene fusions involving NRG1 received afatinib treatment, with response measured by pretreatment and posttreatment PET/CT imaging.Results: Three of 47 (6%) patients with advanced pancreatic ductal adenocarcinoma were identified as KRAS wild type by whole-genome sequencing. All KRAS wild-type tumors were positive for gene fusions involving the ERBB3 ligand NRG1. Two of 3 patients with NRG1 fusion-positive tumors were treated with afatinib and demonstrated a significant and rapid response while on therapy.Conclusions: This work adds to a growing body of evidence that NRG1 gene fusions are recurrent, therapeutically actionable genomic events in pancreatic cancers. Based on the clinical outcomes described here, patients with KRAS wildtype tumors harboring NRG1 gene fusions may benefit from treatment with afatinib.