Whole-genome sequencing reveals the mutational landscape of metastatic small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC)
Whole-genome sequencing reveals the mutational landscape of metastatic small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC)
复制标题
全基因组测序揭示转移性小细胞胆囊神经内分泌癌（GB-SCNEC）的突变情况
DOI：
10.1016/j.canlet.2016.12.027
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发表时间：
2017-04-10
期刊：
影响因子：
9.7
通讯作者：
Liu, Yingbin
中科院分区：
文献类型：
--
作者：
Li, Maolan;Liu, Fatao;Liu, Yingbin
小细胞胆囊神经内分泌癌（GB-SCNEC）是一种相对罕见的胆囊癌组织学类型，在治疗决策中很少考虑GB-SCNEC的基因组分布。我们对一例晚期GB-SCNEC进行了全基因组测序。我们鉴定了大约900种高质量的体细胞单核苷酸变异（SNV）和小插入和缺失（INDEL），其中109种是原发性和转移性肿瘤组织共有的。在原发性和转移性组织标本中均观察到HMCN 1和CDH 10中具有破坏性影响的体细胞非同义编码变异。对SNV和INDEL定位的基因进行通路分析，发现与轴突导向、ERBB信号传导等相关的基因富集。此外，我们还鉴定了11个缺失、4个串联重复和5个倒位定位到已知基因。通过桑格测序，还发现并验证了两个基因融合体，NCAM 2-SGCZ和BTG 3-CCDC 40。此外，我们确定了全基因组拷贝数变异和微卫星不稳定性。在这项研究中，我们确定了GB-SCNEC的新生物标志物，可能作为有价值的预后因素或GB-SCNEC伴淋巴转移患者的治疗反应指标。(C)2017爱思唯尔B. V.保留所有权利。
Small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC) is a relatively rare histological type of gallbladder cancer, and the genomic landscape of GB-SCNEC is rarely considered in treatment decisions. We performed whole-genome sequencing on an advanced case of GB-SCNEC. We identified approximately 900 high-quality somatic single nucleotide variants (SNVs) and small insertions and deletions (INDELs), 109 of which were shared by both the primary and metastatic tumor tissues. Somatic non-synonymous coding variations with damaging impact in HMCN1 and CDH10 were observed in both the primary and metastatic tissue specimens. A pathway analysis of the genes mapped to the SNVs and INDELs revealed gene enrichment associated with axon guidance, ERBB signaling et al. Furthermore, we identified 11 deletions, 4 tandem duplications and 5 inversions that mapped to known genes. Two gene fusions, NCAM2-SGCZ and BTG3-CCDC40 were also discovered and validated by Sanger sequencing. Additionally, we identified genome-wide copy number variations and microsatellite instability. In this study, we identified novel biological markers of GB-SCNEC that may serve as valuable prognostic factors or indicators of treatment response in patients with GB-SCNEC with lymphatic metastasis. (C) 2017 Elsevier B.V. All rights reserved.