Diagnosis, prognosis and treatment of patients with gastrointestinal stromal tumour (GIST) and germline mutation of KIT exon 13

Eur J Cancer. 2013 Jul;49(11):2531-41. doi: 10.1016/j.ejca.2013.04.005. Epub 2013 May 3.


Background: The demonstration of the role of activating mutations of KIT or PDGFRA and the development of targeted therapies have modified the prognosis of patients with gastrointestinal stromal tumours (GISTs). Identification of kindreds with KIT or PDGFRA germline mutation raised new questions, especially regarding the diagnosis, management, monitoring and treatment of these patients.

Methods: We identified index patients of three different families with a KIT exon 13 germline mutation. Pedigree of GIST kindred was assessed in oncogenetic consultation, and medical records were reviewed. Efficacy of imatinib in GISTs with KIT exon 13 was evaluated and compared with published data.

Results: All KIT germline mutations were p.K642E. Twenty affected patients were identified in the three families. GISTs were multiple and occurred before 45years in all but one case. All resected tumours were of spindle cell histology, CD117 positive, and had low or intermediate risk of relapse. Lentigines involving the palms and soles were detected in four patients, and three patients had motrice dysphagia. Nine affected patients died of their disease, all but one before 65years. Affected patients were most often symptomatic and required iterative surgical resections. Imatinib was efficient in GISTs with p.K642E mutation with a disease control rate superior to 90% whatever the sporadic or inherited origin of the tumour.

Conclusions: We propose a regular screening of kindreds who have germline mutation. Treatment with imatinib should be considered for those with symptomatic tumour, larger than 3cm and/or growing rapidly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Benzamides / adverse effects
  • Benzamides / therapeutic use*
  • Exons*
  • Female
  • Gastrointestinal Stromal Tumors / diagnosis
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / enzymology
  • Gastrointestinal Stromal Tumors / genetics*
  • Germ-Line Mutation*
  • Humans
  • Imatinib Mesylate
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / genetics
  • Pedigree
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Prognosis
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Young Adult


  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit