Li Maolan, Liu Fatao, Zhang Yijian, Wu Xiangsong, Wu Wenguang, Wang Xu-An, Zhao Shuai, Liu Shibo, Liang Haibin, Zhang Fei, Ma Qiang, Xiang Shanshan, Li Huaifeng, Jiang Lin, Hu Yunping, Gong Wei, Zhang Yun, Ma Tieliang, Zhang Kai, Liu Yun, Liu Yingbin
Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Dapartment of Hepatobiliary and Laparoscopic Surgrey, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China.
Cancer Lett. 2017 Apr 10;391:20-27. doi: 10.1016/j.canlet.2016.12.027. Epub 2016 Dec 29.
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.
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的基因组格局。我们对一例晚期GB-SCNEC病例进行了全基因组测序。我们鉴定出约900个高质量的体细胞单核苷酸变异（SNV）和小插入缺失（INDEL），其中109个在原发肿瘤组织和转移肿瘤组织中均存在。在原发组织和转移组织标本中均观察到对HMCN1和CDH10有损害影响的体细胞非同义编码变异。对映射到SNV和INDEL的基因进行通路分析，发现基因富集与轴突导向、ERBB信号传导等相关。此外，我们鉴定出11个缺失、4个串联重复和5个倒位，它们映射到已知基因。还发现了两个基因融合体NCAM2-SGCZ和BTG3-CCDC40，并通过桑格测序进行了验证。此外，我们还鉴定出全基因组拷贝数变异和微卫星不稳定性。在本研究中，我们鉴定出GB-SCNEC的新型生物标志物，这些标志物可能作为有价值的预后因素或有淋巴结转移的GB-SCNEC患者治疗反应的指标。
