TY - JOUR
T1 - Diagnosis, prognosis and treatment of patients with gastrointestinal stromal tumour (GIST) and germline mutation of KIT exon 13
AU - Bachet, Jean Baptiste
AU - Landi, Bruno
AU - Laurent-Puig, Pierre
AU - Italiano, Antoine
AU - Le Cesne, Axel
AU - Lévy, Philippe
AU - Safar, Violaine
AU - Duffaud, Florence
AU - Blay, Jean Yves
AU - Emile, Jean François
PY - 2013/7/1
Y1 - 2013/7/1
N2 - 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 45 years 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 65 years. 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 3 cm and/or growing rapidly.
AB - 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 45 years 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 65 years. 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 3 cm and/or growing rapidly.
KW - Gastrointestinal stromal
KW - Germline mutation
KW - Imatinib
KW - KIT
KW - Prognosis
KW - p.K642E
KW - tumour
UR - http://www.scopus.com/inward/record.url?scp=84879290840&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2013.04.005
DO - 10.1016/j.ejca.2013.04.005
M3 - Article
C2 - 23648119
AN - SCOPUS:84879290840
SN - 0959-8049
VL - 49
SP - 2531
EP - 2541
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 11
ER -