Whole-genome sequencing of an advanced case of small-cell gallbladder neuroendocrine carcinoma

The majority of gallbladder cancer cases are discovered at later stages, which frequently leads to poor prognoses. Small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC) is a relatively rare histological type of gallbladder cancer, and its survival rate is exceptionally low because of its greater malignant potential. In addition, the genomic landscape of GB-SCNEC is rarely considered in treatment decisions. We performed whole-genome sequencing on an advanced case of GB-SCNEC. By analyzing the whole-genome sequencing data of the primary cancer tissue (76.29X coverage), lymphatic metastatic cancer tissue (73.92X coverage) and matched non-cancerous tissue (35.73X coverage), we identified approximately 900 high-quality somatic single nucleotide variants (SNVs), 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 revealed gene enrichment associated with axon guidance, ERBB signaling, sulfur metabolism and calcium signaling. Furthermore, we identified 20 chromosomal rearrangements that included 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.