Whole exome sequencing of gastroeneteropancreatic neuroendocrine tumors reveals specific SNV associated with epithelial-mesenchymal transition

Lifshitz Alberto Alegre; Mondragon Oscar Leon; Rodriguez Daniel Marrero; Moises Mercado; Keiko Taniguchi; Claudia Ramirez; Alicia Estrada; la Fuente Mauricio De

doi:10.1530/endoabs.110.P518

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Endocrine Abstracts (2025) 110 P518 | DOI: 10.1530/endoabs.110.P518

ECEESPE2025 Poster Presentations Endocrine Related Cancer (76 abstracts)

Whole exome sequencing of gastroeneteropancreatic neuroendocrine tumors reveals specific SNV associated with epithelial-mesenchymal transition

Alberto Alegre Lifshitz ¹ , Oscar León Mondragón ¹ , Daniel Marrero Rodriguez ¹ , Moises Mercado ¹ , Keiko Taniguchi ¹ , Claudia Ramírez ¹ , Alicia Estrada ¹ & Mauricio De la Fuente ¹

Author affiliations

¹IMSS, Unidad de Investigación en Enfermedades Endocrinas, CDMX, Mexico

JOINT517

Background: Endogenous hyperinsulinemic hypoglycemia is a rare condition which can be caused either by an insulinoma or, less frequently in adults, by nesidioblastosis. A possible origin theory of these is based on a correlation between genetic alterations and metabolic pathways, which could result in an inadequate cell differentiation. This theory has been endorsed by evidence suggesting that dediferenciation has a relation with the pathogenesis of diabetes. Epithelial-mesenchymal-transition (EMT) is a widely explored process in oncology and could be a crucial step relating genetic variants with gastroenteropancreatic neuroendocrine tumors.

Objective: To evaluate genetic variants that could relate EMT with endogenous hyperinsulinism.

Material and methods: Pancreatic tissue from 7 patients was analyzed by means of whole exome sequencing (WES). The pathology diagnosis was nesidioblastosis in five, insulinoma in one, and insulinoma with nesidioblastosis in one.

Results: After searching for single nucleotide variants (SNV) present in more than 50% of the patients, we found the following: FN1 c. A2449C:p. T817P, c. G6688A:p. V2230I (nonsynonymous) and c. G4725A:p. E1575E (synonymous) in 85%; FN1 c. A5691T:p. G1897G and c. T2442A:p. P814P (synonymous) in 71%. CDH1 c. C2253T:p. N751N (synonymous) in 71%. CDH2 c. C2448T:p. A816A and c. C1431G:p. P477P in 85%. MMP2 c. C1806T:p. F602F, c. G1380A:p. T460T in 57%. SNAI1 c. G531A:p. T177T, c. T279C:p. D93D (synonymous) and c. T353C:p. V118A (nonsynonymous) 57%.

Conclusion: Genetic variants for EMT related genes could help to make an association between EMT and endogenous hyperinsulinemia. CDH1, CDH2 MMP2 and FN1 have been previously described in B-Cell dedifferentiation, thus highlighting the importance to understand the molecular mechanisms involved in the pathogenesis of these diseases.