title: Diagnostic criteria, specific mutations, and genetic predisposition in gastrointestinal stromal tumors.
abstract: In 1998, gastrointestinal stromal tumor (GIST) emerged as a distinct oncogenetic entity and subsequently became a paradigm of targeted therapies in solid tumors. Diagnosis of GIST relies on both histology and immunohistochemistry. Ninety-five percent of GISTs express either KIT or DOG-1. Approximately 80%-90% of GISTs harbor gain-of-function mutations of either KIT or platelet-derived growth factor receptor alpha polypeptide (PDGFRA) receptor tyrosine kinase (RTK). More than 100 different mutations have been described, some of which are associated with specific clinical and/or histological characteristics. Detection of KIT or PDGFRA mutations is recommended in advanced GISTs because they are highly predictive of tumor response to RTK inhibitors, as well as in KIT-negative cases to confirm diagnosis. In most cases, GISTs are sporadic, but in rare cases, they are related with genetic predisposition, such as neurofibromatosis type 1, Carney triad, Carney-Stratakis syndrome, and inherited KIT or PDGFRA germline mutations.
authors.affiliation: EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Faculté de médecine PIFO, UVSQ, Guyancourt, France ; Service de Gastroentérologie et Oncologie Digestive, Hôpital Ambroise Paré, APHP, Boulogne, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Bachet
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
keywords: KIT; PDGFRA; gastrointestinal stromal tumors; genetic predispositions; imatinib