Adenomatous polyposis coli gene involvement in ileal enterochromaffin cell neuroendocrine neoplasms

Guido Rindi, Lorena Bottarelli, Cinzia Azzoni, Silvia Pizzi, Tiziana D'Adda, Enrico Maria Silini, Cesare Bordi

Research output: Contribution to journalArticle

12 Citations (Scopus)


The adenomatous polyposis coli gene is a key tumor suppressor gene. Alterations in this gene have been found in most sporadic colon cancers; associated with familial adenomatous polyposis; and found in neoplasms of other organs, such as the liver, stomach, lung, breast, and cerebellar medulloblastoma. In the heterogeneous group of neuroendocrine neoplasms of the gastrointestinal tract, the involvement of adenomatous polyposis coli is debated, and only occasional reports found adenomatous polyposis coli alterations in foregut and midgut neuroendocrine neoplasms, with adenomatous polyposis coli mutations only in the latter. To elucidate the penetrance of adenomatous polyposis coli alterations in ileal neuroendocrine neoplasms, we performed DNA fragment analysis (loss of heterozygosity for 5q22-23 and 5q23) and sequencing on the mutation cluster region of the adenomatous polyposis coli gene on 30 ileal enterochromaffin cell neuroendocrine neoplasms. Adenomatous polyposis coli gene mutations were detected in 23% of cases (7/30); in particular, 57% were missense and 14%, nonsense/frameshift, all novel and different from those reported in colorectal or other cancers. Loss of heterozygosity analysis demonstrated a deletion frequency of 15% (4/27). No association was found with features of tumor progression. Our observations support the involvement of somatic adenomatous polyposis coli alterations in tumorigenesis of ileal enterochromaffin cell neuroendocrine neoplasms; the mechanisms of adenomatous polyposis coli gene inactivation appear to be different from those reported in other tumor types.
Original languageEnglish
Pages (from-to)2736-2742
Number of pages7
JournalHuman Pathology
Publication statusPublished - 2013


  • APC
  • Adenomatous Polyposis Coli Protein
  • Adult
  • Aged
  • Aged, 80 and over
  • Allelic losses
  • DNA Mutational Analysis
  • Enterochromaffin Cells
  • Female
  • Genes, APC
  • Humans
  • Ileal Neoplasms
  • Ileal neuroendocrine neoplasms
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Mutation
  • Neuroendocrine Tumors
  • Polymorphism
  • Signal Transduction
  • beta Catenin


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