%0 Journal Article
%T Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications
%A Michael A Postow
%A Mark E Robson
%J Clinical Sarcoma Research
%D 2012
%I BioMed Central
%R 10.1186/2045-3329-2-16
%X Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors arising in the gastrointestinal tract [1,2]. Though the majority of GISTs appear to arise sporadically, a number of families with high frequencies of GISTs have been reported and germline mutations have been identified [3]. The true frequency of all GIST diagnoses has been difficult to determine because the definition of GIST was derived in 1990 before it was molecularly characterized. One United States report from the Surveillance, Epidemiology, and End Results (SEER) database indicated that, from 1992 to 2000, the yearly incidence rate in the United States was 6.8 cases per million [4]. The reported US annual incidence rate is slightly lower than incidence rates reported in several international epidemiological studies with highest described incidence of 14.5 cases per million in Sweden [5-7]. Discrepancies between diagnostic criteria over the time period of data collection may have accounted for some of the variation. No specific epidemiological risk factors for GIST have been described.The majority of GISTs appear to be sporadic, but a number of families with inherited predisposition to GISTs have been identified. The first family with features consistent with inherited GIST was reported in 1990, but it was not until 1998 that Nishida and colleagues identified the first germline mutation associated with familial predisposition to GIST [8,9]. In this Japanese family, three individuals in two generations were diagnosed with multiple GISTs. The germline DNA of the available affected family members contained a mutation in exon 11 of c-KIT, which resulted in deletion of a valine residue at codon 559_560 in the juxta-membrane domain of the KIT protein. This same mutation was observed in the subjects¡¯ GIST tumors and resulted in constitutive activation of KIT.Since this first description of a family with an exon 11 KIT mutation, multiple other families with inherited GIST syndromes have been
%K Gastrointestinal stromal tumor
%K c-KIT
%K Platelet-derived growth factor-alpha
%K Neurofibromatosis
%K Carney triad
%K Carney-stratakis syndrome
%K Succinate dehydrogenase
%U http://www.clinicalsarcomaresearch.com/content/2/1/16