Suppressor gene alterations in the colorectal adenoma‐carcinoma sequence

Kathleen R. Cho, Bert Vogelstein

Research output: Contribution to journalArticlepeer-review

Abstract

Tumorigenesis is thought to be a multistep process in which genetic alterations accumulate to bring about the neoplastic phenotype. Colorectal tumors appear to arise as a result of the mutational activation of oncogenes coupled with the inactivation of several tumor suppressor genes. We have found frequent allelic deletions of specific portions of chromosomes 5, 17, and 18 which presumably harbor suppressor genes. The target of allelic loss events on chromosome 17 has been shown to be the p53 gene, which is frequently mutated not only in colon cancer but in several other tumor types as well. Candidate suppressor genes have also recently been identified on chromosomes 18 and 5. The DCC gene on chromosome 18q encodes a protein with significant sequence similarity to neural cell adhesison molecules and other related cell surface glycoproteins. Alterations of this gene may interfere with normal cell growth and differentiation by disrupting cell‐cell or cell‐substrate interactions. Two genes (MCC and APC) on chromosome 5q have also recently been identified and partially cloned. These genes are located in a region tightly linked to familial adenomatous polyposis (FAP). While MCC mutations have been found only in sporadic colon tumors, APC mutations have been identified in sporadic tumors as well as the germline of patients with FAP. Studies are currently in progress to increase our understanding of how alterations of these genes affect colorectal tumor cell growth. © 1992 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)137-141
Number of pages5
JournalJournal of cellular biochemistry
Volume50
Issue numberS16G
DOIs
StatePublished - 1992

Keywords

  • APC
  • DCC
  • MCC
  • chemoprevention
  • colorectal tumors
  • familial adenomatous polyposis (FAP)
  • intermediate biomarker
  • p53
  • tumor suppressor genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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