title: Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations.
abstract: Most gastrointestinal stromal tumors (GIST) have activating mutations in either KIT or PDGFRA. However, a small subset of GIST lacks either mutation. To investigate the molecular characteristics of GIST according to mutation type, protein expression profiles in 12 GIST (2 cases with PDGFRA mutations, 8 cases with KIT mutations and 2 cases lacking either mutation) were analyzed using 2-DE and MALDI-TOF-MS. Comparative analysis of the respective spot patterns using 2-DE showed that 15 proteins were differently expressed according to the mutation status. Expression levels of septin and heat shock protein (HSP) 27 were increased in GIST with KIT mutations and annexin V was overexpressed in GIST lacking either mutation. Among the 15 proteins, overexpression of 5 proteins [annexin V, high mobility group protein 1 (HMGB1), C13orf2, glutamate dehydrogenase 1 and fibrinogen beta chain] and decreased expression of RoXaN correlated with a higher tumor grade. These findings suggest that differential protein expression can be used as a diagnostic biomarker. Moreover, it may play a role in the development and progression of GIST according to activating mutation type, as these proteins have been shown to be involved in tumor metastasis, apoptosis and immune response.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Kang
authors.forename: Kwi Hye
authors.initials: KH
authors.lastname: Koh
authors.forename: Eungi
authors.initials: E
authors.lastname: Yang
authors.forename: Kwon Tae
authors.initials: KT
authors.lastname: You
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Paik
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
mesh_terms: D015180:Electrophoresis, Gel, Two-Dimensional; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011446:Prospective Studies; D040901:Proteomics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha