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Title: Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients
Authors: Maertens, Ophélia ×
Prenen, Hans
Debiec-Rychter, Maria
Wozniak, Agnieszka
Sciot, Raphael
Pauwels, Patrick
De Wever, Ivo
Vermeesch, Joris
De Raedt, Thomas
De Paepe, Anne
Speleman, Frank
Van Oosterom, Allan
Messiaen, Ludwine
Legius, Eric #
Issue Date: Mar-2006
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:15 issue:6 pages:1015-1023
Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. KIT and PDGFRA activating mutations are the oncogenic mechanisms in most sporadic GISTs. In addition to sporadic occurrences, GISTs are increasingly being recognized in association with neurofibromatosis type 1 (NF1), yet the underlying pathogenic mechanism remains elusive. To gain an insight into the mechanisms underlying GIST formation in NF1 patients, we studied seven GISTs from three NF1 patients with a combination of different techniques: mutation analysis (KIT, PDGFRA and NF1), western blotting, array CGH and ex vivo imatinib response experiments. We demonstrate that (i) the NF1-related GISTs do not have KIT or PDGFRA mutations, (ii) the molecular event underlying GIST development in this patient group is a somatic inactivation of the wild-type NF1 allele in the tumor and (iii) inactivation of neurofibromin is an alternate mechanism to (hyper) activate the MAP-kinase pathway, while the JAK-STAT3 and PI3K-AKT pathways are less activated in NF1-related GIST compared with sporadic GISTs. In conclusion, we report for the first time the molecular pathogenesis of GISTs in NF1 individuals and demonstrate that this type of tumor clearly belongs to the spectrum of clinical symptoms in NF1.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Laboratory of Experimental Oncology
Surgical Oncology
Department of Oncology - miscellaneous
Translational Cell & Tissue Research
Laboratory for Genetics of Malignant Disorders
Clinical Digestive Oncology (+)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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