Gastrointestinal stromal tumors: their origin and cause

Int J Clin Oncol. 2001 Feb;6(1):1-5. doi: 10.1007/pl00012072.


Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, we found that GISTs expressed KIT, a receptor tyrosine kinase encoded by the protooncogene c-kit. We propose that GISTs may originate from interstitial cells of Cajal (ICCs), which are considered to be pacemaker cells for the autonomous movement of the gastrointestinal tract. There are major two reasons for this proposal: one is that both GISTs and ICCs are double-positive for KIT and CD34, and the other is that multiple GISTs appear to develop from diffuse ICC hyperplasia in germline mutations of the c-kit gene. Because somatic gain-of-function mutations of the c-kit gene are observed in solitary GISTs, and because the germline gain-of-function mutations of the c-kit gene are observed in familial and multiple GISTs, the gain-of function mutations of the c-kit gene are considered to be a cause of the development of GISTs.

Publication types

  • Review

MeSH terms

  • Antigens, CD34 / analysis
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / physiopathology*
  • Germ-Line Mutation
  • Humans
  • Neoplasms, Connective Tissue / genetics*
  • Neoplasms, Connective Tissue / physiopathology*
  • Proto-Oncogene Proteins c-kit / analysis
  • Proto-Oncogene Proteins c-kit / genetics*
  • Stromal Cells / pathology


  • Antigens, CD34
  • Proto-Oncogene Proteins c-kit