Inactivation of both APC alleles in an early stage of colon adenomas in a patient with familial adenomatous polyposis (FAP)

Hum Mol Genet. 1992 Sep;1(6):387-90. doi: 10.1093/hmg/1.6.387.


To examine whether the dosage effect of germ-line mutations in patients with familial adenomatous polyposis (FAP) is sufficient to cause colorectal adenomas, or an additional somatic mutation of the normal allele is required as well, we have investigated somatic mutations of the APC gene in multiple adenomas developed in one FAP patient. In addition to a 5-bp deletion of one allele present constitutionally in this patient, the normal APC allele had been lost in five of seven DNA samples extracted from small adenomas (< 3 mm in diameter) with mild or moderate atypia. This result indicates that the inactivation of both alleles of the APC gene is probably essential for the development of an early-stage adenoma, in agreement with the two-hit mutational model underlying the concept of tumor suppressor genes.

Publication types

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

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology
  • Adenomatous Polyposis Coli / genetics*
  • Adult
  • Alleles
  • Base Sequence
  • Chromosomes, Human, Pair 5
  • Cloning, Molecular / methods
  • Colon / pathology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • DNA / blood
  • DNA / genetics
  • DNA / isolation & purification
  • Female
  • Frameshift Mutation
  • Genes, APC*
  • Humans
  • Intestinal Mucosa / pathology
  • Leukocytes / physiology
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • Rectal Neoplasms / genetics*


  • Oligodeoxyribonucleotides
  • DNA