Chapter 18. Gastrointestinal Stromal Tumors (GISTs)

  1. Prof. Dr. Heike Allgayer PhD2,
  2. Prof. Dr. Helga Rehder3 and
  3. Prof. Dr. Simone Fulda4
  1. Maria Debiec-Rychter

Published Online: 21 AUG 2009

DOI: 10.1002/9783527627523.ch18

Hereditary Tumors: From Genes to Clinical Consequences

Hereditary Tumors: From Genes to Clinical Consequences

How to Cite

Debiec-Rychter, M. (2008) Gastrointestinal Stromal Tumors (GISTs), in Hereditary Tumors: From Genes to Clinical Consequences (eds H. Allgayer, H. Rehder and S. Fulda), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527627523.ch18

Editor Information

  1. 2

    University of Heidelberg and DKFZ (German Cancer Research Center) Heidelberg, Medical Faculty Mannheim, Chair of Experimental Surgery, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany

  2. 3

    Medical University Vienna, Department of Medical Genetics, Währinger Strasse 10, 1090 Wien, Austria

  3. 4

    Ulm University Children's Hospital, Eythstrasse 24, 89075 Ulm, Germany

Author Information

  1. Catholic University of Leuven, Center for Human Genetics, Herestraat 49, 3000 Leuven, Belgium

Publication History

  1. Published Online: 21 AUG 2009
  2. Published Print: 17 DEC 2008

ISBN Information

Print ISBN: 9783527320288

Online ISBN: 9783527627523



  • Carney–Stratakis syndrome;
  • Carney triad;
  • gastrointestinal stromal tumors;
  • hyperpigmentation;
  • interstitial cells of Cajal;
  • KIT mutation;
  • tyrosine kinase


Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract (GI), evolve from a progenitor related to the interstitial cells of Cajal (ICC). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs.

Familial GIST syndrome is an autosomal dominant genetic disorder with germline mutations of the KIT or PDFGRA gene as an underlying cause of the disease. Familial GIST syndrome associated with a germline KIT mutation is characterized by multiple GISTs associated with hyperplasia of ICCs, and other clinicopathologic features, such as skin hyperpigmentation, GI motility dysfunctions, or mast cell abnormalities. Symptoms associated with GI bleeding are common, and may be the only manifestation of the disease. Germline PDGFRA mutations result in multiple GISTs, diffuse hyperplasia of ICCs, and GI dysmotility symptoms, but affected kindreds lack pigmentation or mast cells abnormalities.

Hereditary forms of the disease also arise in the settings of other hereditary syndromes, such as neurofibromatosis type 1 (NF1), the Carney–Stratakis syndrome, and the Carney triad. GIST development in patients with NF1 is caused by a somatic inactivation of the wildtype NF1 allele in the tumor and the absence of neurofibromin, resulting in hyperactivation of the signaling pathway downstream of KIT. Familial Carney–Stratakis syndrome is the dyad of multifocal, gastric GISTs and paragangliomas, transmitted as an autosomal-dominant trait with incomplete penetrance. The condition is caused by germline “loss-of function” mutations in the succinate dehydrogenase subunit B (SDHB), C (SDHC), or D (SDHD) genes. The association of gastric, multiple GISTs, with pulmonary chondromas and functional paragangliomas is known as the Carney triad. The genetic basis of the association is yet unknown.

Familial GISTs usually have a milder clinical course than sporadic cases. Imatinib mesylate may be effective in the prevention of development as well as in the treatment of hereditary GISTs.