An experimental study led by Pompeu Fabra University and in which the Pancreas Regeneration  group has participated, describes the mechanism whereby insulinomas, a rare type of neuroendocrine tumour that affects pancreatic beta cells. According to the study, insulinomas are the result of the accumulation of rare mutations that lead to a homogeneous change in the epigenetic profile of pancreatic beta cells. This profile change causes beta cells to express unusually high levels of oncogenes, growth and transcription factors, and genes related to insulin production.

Insulinomas are rare pancreatic neuroendocrine tumours that involve the excessive growth of beta cells, which are responsible for secreting insulin. Often, they are diagnosed because they involve excessive insulin production that usually leads to hypoglycaemia. Each year, four people in one million are diagnosed with insulinomas, and in most cases, they are benign. If detected early and surgically removed, they have a good prognosis and only about in one in ten insulinomas are malignant.

In a study published today in the journal Cell Genomics, a mechanism whereby beta cells undergo a transformation towards a neoplastic phenotype is proposed for the first time. “This is the accumulation of rare mutations that converge in a change in the epigenetic profile of beta cells”, explains Mireia Ramos, co-first author of the study. These mutations vary among the 42 insulinomas analysed, and most accumulate in regulatory regions of the genome.

This new epigenetic profile causes tumour beta cells to lose their repression marks and, unlike healthy beta cells, have a series of active oncogenes, growth and transcription factors and genes related to insulin production, which alter their function.

Published originally in UPF website