title: The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status.
abstract: We recently characterized gene expression patterns in gastrointestinal stromal tumors (GISTs) using cDNA microarrays, and found that the gene FLJ10261 (DOG1, discovered on GIST-1), encoding a hypothetical protein, was specifically expressed in GISTs. The immunoreactivity of a rabbit antiserum to synthetic DOG1 peptides was assessed on two soft tissue tumor microarrays. The tissue microarrays included 587 soft tissue tumors, with 149 GISTs, including 127 GIST cases for which the KIT and PDGFRA mutation status was known. Immunoreactivity for DOG1 was found in 136 of 139 (97.8%) of scorable GISTs. All seven GIST cases with a PDGFRA mutation were DOG1-positive, while most of these failed to react for KIT. The immunohistochemical findings were confirmed with in situ hybridization probes for DOG1, KIT, and PDGFRA. Other neoplasms in the differential diagnosis of GIST, including desmoid fibromatosis (0 of 17) and Schwannoma (0 of 3), were immunonegative for DOG1. Only 4 of 438 non-GIST cases were immunoreactive for DOG1. DOG1, a protein of unknown function, is expressed strongly on the cell surface of GISTs and is rarely expressed in other soft tissue tumors. Reactivity for DOG1 may aid in the diagnosis of GISTs, including PDGFRA mutants that fail to express KIT antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase.
authors.affiliation: Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: Subbaya
authors.initials: S
authors.lastname: Subramanian
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Shirley
authors.initials: S
authors.lastname: Zhu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Ball
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Rajiv
authors.initials: R
authors.lastname: Patel
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
mesh_terms: D000075369:Anoctamin-1; D015415:Biomarkers / Q000032:analysis*; D018118:Chloride Channels; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000032:analysis*; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis*; D020411:Oligonucleotide Array Sequence Analysis; D010744:Phosphoric Monoester Hydrolases; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D015415:Biomarkers; D018118:Chloride Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C093600:DOG2 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases