Endocrine tumours of the gastrointestinal tract: aetiology, molecular pathogenesis and genetics

Best Pract Res Clin Gastroenterol. 2005 Aug;19(4):519-34. doi: 10.1016/j.bpg.2005.03.005.

Abstract

Endocrine tumours of the gut and pancreas originate from cells of the diffuse endocrine system and are characterised by the production of a wide variety of bioactive substances including growth factors. Two major tumour categories are distinguished-well-differentiated and poorly differentiated neoplasms-with distinct phenotypes and significantly diverse clinical behaviour. Here, genetic background data are summarised on an anatomical basis for tumours of foregut, midgut and hindgut derivatives. For well-differentiated tumours, independent techniques identified the abnormality of multiple chromosomal sites and genes, pointing to a complex genetic background. Differences in foregut tumours compared with midgut and hindgut tumours are, however, outlined. The multiple endocrine neoplasia syndrome type 1 (MEN1) gene is reported to be involved in about one-third of sporadic foregut endocrine tumours and exceptionally in midgut and hindgut tumours. Similarly, X chromosome markers are associated with malignant behaviour in foregut tumours only. For poorly differentiated carcinomas, a high degree of chromosomal instability is the common genetic trait independent of tumour site and frequently involving the p53 gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Neuroendocrine / genetics*
  • Carcinoma, Neuroendocrine / pathology
  • Cell Differentiation
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / pathology
  • Genes, Tumor Suppressor / physiology
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity
  • Methylation
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Phenotype
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology
  • Transforming Growth Factors / physiology
  • Tumor Suppressor Proteins / genetics

Substances

  • MEN1 protein, human
  • Proto-Oncogene Proteins
  • RASSF1 protein, human
  • Tumor Suppressor Proteins
  • Transforming Growth Factors