ArticleSignal transduction and targeted therapy2021
Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Macrophage-rich niches regulate T cell dynamics at the liver invasive margin during gallbladder cancer progression.The Journal of clinical investigation · 2026Article
- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
- Whole-Exome Profiling of Epstein-Barr Virus-Positive Neuroendocrine Carcinoma of the Nasopharynx.Endocrine pathology · 2026Article
- Two cases of large cell neuroendocrine carcinoma of the gallbladder: case reports and systemic literature review.Frontiers in medicine · 2026Article
- Comprehensive genomic profiling of neuroendocrine neoplasms of the colorectum.Frontiers in genetics · 2026Article
- DDX11 interacts with PARP1 to facilitate PARylation, thereby promoting gallbladder cancer progression and conferring gemcitabine resistance.Acta biochimica et biophysica Sinica · 2025Article
- Clinicopathologic and molecular characteristics of neuroendocrine carcinomas of the gallbladder.Histology and histopathology · 2025Article
- Targeted gene sequencing and bioinformatics analysis of patients with gallbladder neuroendocrine carcinoma: A case report.World journal of gastrointestinal oncology · 2025Article
- Gallbladder large cell neuroendocrine carcinoma in a patient with multiple myeloma: a case report and literature review.Frontiers in oncology · 2025Article
- Case Report: Deep and durable response to talazoparib in germlineFrontiers in oncology · 2025Article
- Case Report: Diagnosing and treating gallbladder neuroendocrine neoplasms through comparative analysis: a case series and literature review.Frontiers in oncology · 2025Article
- Super-Enhancer Reprograming Driven by SOX9 and TCF7L2 Represents Transcription-Targeted Therapeutic Vulnerability for Treating Gallbladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?Frontiers in endocrinology · 2024Article
- Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.Cancer metastasis reviews · 2023Review
- Gastric neuroendocrine tumors in aWorld journal of gastrointestinal oncology · 2023Article
- ELF3 promotes gemcitabine resistance through PKMYT1/CDK1 signaling pathway in gallbladder cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Comprehensive Clinical Analysis of Gallbladder Neuroendocrine Neoplasms: A Large-Volume Multicenter Study During One Decade.Annals of surgical oncology · 2022Article
- Novel protein kinase inhibitor TT-00420 inhibits gallbladder cancer by inhibiting JNK/JUN-mediated signaling pathway.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Expanding Therapeutic Opportunities for Extrapulmonary Neuroendocrine Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience.Current issues in molecular biology · 2022Article
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Authors and funding
17 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) is a rare but extremely malignant subtype of gallbladder cancer (GBC). The genetic and molecular signatures of GB-NEC are poorly understood; thus, molecular targeting is currently unavailable. In the present study, we applied whole-exome sequencing (WES) technology to detect gene mutations and predicted somatic single-nucleotide variants (SNVs) in 15 cases of GB-NEC and 22 cases of general GBC. In 15 GB-NECs, the C > T mutation was predominant among the 6 types of SNVs. TP53 showed the highest mutation frequency (73%, 11/15). Compared with neuroendocrine carcinomas of other organs, significantly mutated genes (SMGs) in GB-NECs were more similar to those in pulmonary large-cell neuroendocrine carcinomas (LCNECs), with driver roles for TP53 and RB1. In the COSMIC database of cancer-related genes, 211 genes were mutated. Strikingly, RB1 (4/15, 27%) and NAB2 (3/15, 20%) mutations were found specifically in GB-NECs; in contrast, mutations in 29 genes, including ERBB2 and ERBB3, were identified exclusively in GBC. Mutations in RB1 and NAB2 were significantly related to downregulation of the RB1 and NAB2 proteins, respectively, according to immunohistochemical (IHC) data (p values = 0.0453 and 0.0303). Clinically actionable genes indicated 23 mutated genes, including ALK, BRCA1, and BRCA2. In addition, potential somatic SNVs predicted by ISOWN and SomVarIUS constituted 6 primary COSMIC mutation signatures (1, 3, 30, 6, 7, and 13) in GB-NEC. Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch, WNT, Hippo, and RTK-RAS pathways. In summary, we have systematically identified the mutation landscape of GB-NEC, and these findings may provide mechanistic insights into the specific pathogenesis of this deadly disease.
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