Authors' recommendations: Gastrointestinal stromal tumors (GISTs) are the most common tumors of mesenchymal origin, although they are rare, with a prevalence of just 10 to 15 per million individuals. GISTs may occur anywhere within the gastrointestinal (GI) tract, with the most common locations being the stomach, jejunum, and ileum. The malignancy of GISTs is variable, but is highest for small intestine GISTs at 40% to 50%. GISTs can be detected through clinical symptoms, such as fatigue, dyspepsia, and acute or chronic GI bleeding, or incidentally through surgery, imaging studies, or endoscopy. GISTs are usually found in patients who are 40 years of age or older; however, 5% to 20% are found in younger individuals and are often associated with syndromes such as neurofibromatosis type 1 (NF1), Carney-triad syndrome, Carney-Stratakis syndrome, and familial GIST. The vast majority of GISTs occur sporadically. In the late 1990s it was observed that GISTs typically express the CD117 protein, which is encoded by the v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog gene known as KIT. The CD117 protein is a type III tyrosine kinase receptor, and GIST tumors often have sequence variants in the KIT gene that result in a gain of function of the CD117 protein. Most GISTs test positive for CD117 immunostaining, indicating expression of the KIT gene. A second gene associated with GISTs is the platelet-derived growth factor receptor, alpha polypeptide gene (PDGFRA). PDGFRA is located next to KIT on chromosome 4 and may be an ancestral gene duplication of KIT. The PDGFRA protein is also a tyrosine kinase receptor and probably functions similarly to CD117. Sequence variants in KIT and PDGFRA appear to be mutually exclusive, which suggests that sequence variants in these genes are key in the development of the tumors. Some patients have GISTs that do not have KIT or PDGFRA sequence variants; these are called wildtype GISTs. Treatment of GISTs is with surgery if the tumor is resectable, with the aim of surgery being to completely remove the tumor and any marginal tissue without rupture. For patients with more advanced disease that has spread to nearby lymph nodes or has metastasized, the tumor may only be partially resectable or might not be resectable at all. GISTs are relatively unresponsive to traditional chemotherapeutic agents. However, treatment of GISTs has been revolutionized by the discovery that the tyrosine kinase inhibitors (TKIs) imatinib mesylate (Gleevec®/Glivec®; Novartis Pharmaceuticals Corp.) and sunitinib malate (Sutent®; Pfizer Inc.) are often effective at increasing survival time of patients with GISTs. This report focuses on the use of KIT and PDGFRA molecular analysis to guide primary treatment options with TKIs for GIST.

Project Status: Completed

Year Published: 2011

URL for published report: URL http://www.hayesinc.com/hayes/crd/?crd=12952

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2011 Winifred S. Hayes, Inc