ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2018
Mutational landscape of goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix is distinct from typical carcinoids and colorectal adenocarcinomas.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 62 citations in OpenAlex.
- A paired sequencing study of goblet cell adenocarcinomas with coincident sessile serrated lesions and low-grade appendiceal mucinous neoplasms.Virchows Archiv : an international journal of pathology · 2025Article
- The Genomic Topography of Appendiceal Cancers: Our Current Understanding, Clinical Perspectives, and Future Directions.Cancers · 2025Review
- Defining a 'cells to society' research framework for appendiceal tumours.Nature reviews. Cancer · 2025Review
- Mutational Features and Tumor Microenvironment Alterations in High-Grade Appendiceal Cancers Treated With Iterative Hyperthermic Intraperitoneal Chemotherapy.JCO precision oncology · 2024Article
- Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei).Annals of surgical oncology · 2023Article
- The Vermiform Appendix and Its Pathologies.Cancers · 2023Review
- Review
- Landscape of Genetic Mutations in Appendiceal Cancers.Cancers · 2023Review
- Appendiceal Goblet Cell Carcinoma: Role of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).Indian journal of surgical oncology · 2023Review
- Molecular Landscape and Association With Crohn Disease of Poorly Cohesive Carcinomas of the Nonampullary Small Bowel.American journal of clinical pathology · 2023Article
- Genetic alterations in gastric amphicrine carcinomas and comparison with gastric mixed neuroendocrine-non-neuroendocrine neoplasms.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Goblet Cell Adenocarcinoma of the Appendix: A Systematic Review and Incidence and Survival of 1,225 Cases From an English Cancer Registry.Frontiers in oncology · 2022Article
- Histologic and Racial/Ethnic Patterns of Appendiceal Cancer among Young Patients.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- New insights in the pathology of peritoneal surface malignancy.Journal of gastrointestinal oncology · 2021Review
- Molecular Characterization of Appendiceal Goblet Cell Carcinoid.Molecular cancer therapeutics · 2020Article
- Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset.JAMA network open · 2020Article
- Duodenal Obstruction Caused by the Long-term Recurrence of Appendiceal Goblet Cell Carcinoid.Internal medicine (Tokyo, Japan) · 2020Article
- Knowledge gaps in the appendix: a multi-institutional study from seven academic centers.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Neuroendocrine Markers Insulinoma-Associated Protein 1, Chromogranin, Synaptophysin, and CD56 Show Rare Positivity in Adenocarcinoma Ex-Goblet Cell Carcinoids.Gastroenterology research · 2019Article
- Genomic Landscape of Appendiceal Neoplasms.JCO precision oncology · 2018Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is limited data on the spectrum of molecular alterations in goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix. We used next generation sequencing to determine mutations of potential pathogenetic and therapeutic significance in this rare group of tumors. Adequate DNA was successfully extracted in 34/46 cases and the final group included 18 goblet cell carcinoids and 16 adenocarcinoma ex goblet cell carcinoids. Illumina TruSeq™ was used for sequencing exons of a custom 282 gene panel using an Illumina HiSeq 2000. All cases had a minimum coverage depth of at least 50 reads. After filtering through the Exome Sequencing Project, the number of mutations per case ranged from 0-9 (mean:3). The mutational burden in adenocarcinoma ex goblet cell carcinoids was significantly higher than goblet cell carcinoids (mean 5 vs. 3; p < 0.05) but the spectrum of alterations overlapped between the two groups. The most frequent mutations included ARID1A (4/34), ARID2 (4/34), CDH1 (4/34), RHPN2 (4/34), and MLL2 (3/34). Some mutations typically seen in conventional colorectal adenocarcinomas were also identified but with much lower frequency (APC :4/34; KRAS :2/34). MLL2 and KRAS mutations were only seen in adenocarcinoma ex goblet cell carcinoids and TP53 mutations were limited to poorly differentiated adenocarcinoma ex goblet cell carcinoids (2/34). Copy number changes could be evaluated in 15/34 cases and showed low copy number gains in CDKN1B (6/15) and NFKBIA (6/15), among others. The overlapping molecular alterations suggest that goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids are best considered two grades of differentiation of the same tumor rather than two distinct histological types. Mutations in TP53, CDH1 and MLL2 mutations were predominantly present in the adenocarcinoma ex goblet cell carcinoid group consistent with transformation to a higher grade lesion. The unique mutational profile also offers an explanation for the poor chemosensitivity in these tumors and highlights the need for developing new targeted therapies.
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