Genomic spectra of biliary tract cancer
Genomic spectra of biliary tract cancer
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DOI：
10.1038/ng.3375
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发表时间：
2015-09-01
期刊：
影响因子：
30.8
通讯作者：
Shibata, Tatsuhiro
中科院分区：
文献类型：
--
作者：
Nakamura, Hiromi;Arai, Yasuhito;Shibata, Tatsuhiro
胆道癌（BTC），包括肝内（ICC）和肝外（ECC）胆管癌和胆囊癌的发病率在全球范围内增加;然而，目前尚未批准有效的靶向分子治疗。在这里，我们对260种BTC进行了分子表征，并发现了包括新的潜在治疗靶点在内的基因组改变谱。在胆囊癌和ECC中观察到具有较高APOBEC相关突变特征负荷的突变特征的梯度谱。包括ELF 3在内的32个显著改变的基因被鉴定出来，近40%的病例具有靶向遗传改变。涉及FGFR 2和PRKACA或PRKACB的基因融合分别优先发生在ICC和ECC中，并且可操作的生长因子介导的信号的亚型相关患病率值得注意。预后最差的亚组具有高度突变肿瘤的显著富集和免疫检查点分子表达的特征性升高。因此，免疫调节疗法也可能是这些患者潜在的有希望的选择。
The incidence of biliary tract cancer (BTC), including intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma and gallbladder cancer, has increased globally; however, no effective targeted molecular therapies have been approved at the present time. Here we molecularly characterized 260 BTCs and uncovered spectra of genomic alterations that included new potential therapeutic targets. Gradient spectra of mutational signatures with a higher burden of the APOBEC-associated mutation signature were observed in gallbladder cancer and ECC. Thirty-two significantly altered genes, including ELF3, were identified, and nearly 40% of cases harbored targetable genetic alterations. Gene fusions involving FGFR2 and PRKACA or PRKACB preferentially occurred in ICC and ECC, respectively, and the subtype-associated prevalence of actionable growth factor-mediated signals was noteworthy. The subgroup with the poorest prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules. Accordingly, immune-modulating therapies might also be potentially promising options for these patients.