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Whole-genome sequencing reveals the mutational landscape of metastatic small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC)
Journal article   Peer reviewed

Whole-genome sequencing reveals the mutational landscape of metastatic small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC)

Maolan Li, Fatao Liu, Yijian Zhang, Xiangsong Wu, Wenguang Wu, Xu-An Wang, Shuai Zhao, Shibo Liu, Haibin Liang, Fei Zhang, …
Cancer letters, v 391, pp 20-27
10 Apr 2017
PMID: 28040546

Abstract

Gallbladder cancer Small-cell gallbladder neuroendocrine carcinoma Variation Whole-genome sequencing
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. •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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
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