Whole-genome sequencing reveals the mutational landscape of metastatic small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC). (10th April 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Cancer letters. Volume 391(2017)
• Page Start: 20
• Page End: 27
• Publication Date: 2017-04-10
• Subjects: Small-cell gallbladder neuroendocrine carcinoma -- Gallbladder cancer -- Whole-genome sequencing -- Variation; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.12.027
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: The incidence of GB-SCNEC is extremely low with poor prognosis. This study firstly examined the whole-genome somatic mutations of an advanced GB-SCNEC case. Non-silent variations in HMCN1 and CDH10 were observed in both the primary and metastatic tumors. The mutant genes of GB-SCNEC were enriched with ERBB signaling pathway and axon guidance et al. Structure variations, copy number variations and MSI instabilities were also observed.