Evidence for genomic instability in human colonic aberrant crypt foci

Leonard H. Augenlicht, Christine Richards, Georgia Corner, Theresa P. Pretlow

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Aberrant crypt foci (ACF) are morphologically abnormal structures that can be identified in whole mounts of colonic tissue from rodents treated with colon carcinogens and from patients at risk for development of colon tumors. ACF are heterogeneous and exhibit properties, such as altered patterns of cell proliferation, the presence of dysplasia, and mutations in protooncogenes and tumor suppressor genes, consistent with the hypothesis that a subset of these structures are precursors to tumor formation. In this study, we have investigated the presence of genomic instability in DNA isolated from human ACF from patients with colon cancer. Altered allele length detected by electrophoretic separation of PCR amplified oligo A or microsatellite loci was used to identify candidate samples which were then more rigorously investigated by sequence analysis for instability. Of 20 patients examined, two exhibited alterations at two loci, and this instability could be confirmed by sequence analysis. An additional seven of the 20 patients had evidence for instability at a single locus. Quantitative sequence analysis of the DNA from an ACF of one of these seven patients was consistent with alteration of allele length in this patient, but the alteration was not sufficiently different from normal to reach statistical significance. Thus, genomic instability, manifest as altered length of microsatellite and oligo A sequences, is present in some ACE, and therefore can be a very early event in the development of some human colon cancers.

Original languageEnglish (US)
Pages (from-to)1767-1772
Number of pages6
JournalOncogene
Volume12
Issue number8
StatePublished - 1996

Keywords

  • Aberrant crypt foci
  • Colon cancer precursors
  • Genomic instability
  • Premalignant lesions

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Evidence for genomic instability in human colonic aberrant crypt foci'. Together they form a unique fingerprint.

Cite this