title: Whole-genome sequencing reveals the mutational landscape of metastatic small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC).
abstract: 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.
authors.affiliation: 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.
authors.forename: Maolan
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Fatao
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yijian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xiangsong
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Xu-An
authors.initials: XA
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Shibo
authors.initials: S
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Haibin
authors.initials: H
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xiang
authors.affiliation: 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.
authors.forename: Huaifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Dapartment of Hepatobiliary and Laparoscopic Surgrey, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Dapartment of Hepatobiliary and Laparoscopic Surgrey, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China.
authors.forename: Tieliang
authors.initials: T
authors.lastname: Ma
authors.affiliation: Dapartment of Hepatobiliary and Laparoscopic Surgrey, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China. Electronic address: zk_104@163.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China. Electronic address: superliuyun@fudan.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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. Electronic address: liuybphd@126.com.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D018278:Carcinoma, Neuroendocrine / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D005706:Gallbladder Neoplasms / Q000235:genetics*; D016678:Genome; D006801:Humans; D009362:Neoplasm Metastasis; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: Gallbladder cancer; Small-cell gallbladder neuroendocrine carcinoma; Variation; Whole-genome sequencing