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(American Journal of Pathology. 2004;165:107-113.)
© 2004 American Society for Investigative Pathology

The Novel Marker, DOG1, Is Expressed Ubiquitously in Gastrointestinal Stromal Tumors Irrespective of KIT or PDGFRA Mutation Status

Robert B. West*, Christopher L. Corless{dagger}, Xin Chen{ddagger}, Brian P. Rubin§, Subbaya Subramanian*, Kelli Montgomery*, Shirley Zhu*, Catherine A. Ball, Torsten O. Nielsen||, Rajiv Patel**, John R. Goldblum**, Patrick O. Brown{ddagger}§§, Michael C. Heinrich{dagger}{dagger} and Matt van de Rijn*

From the Departments of Pathology,* Genetics, and Biochemistry,{ddagger} and Howard Hughes Medical Institute,§§ Stanford University Medical Center, Stanford, California; the Departments of Pathology{dagger} and Medicine,{dagger}{dagger} Oregon Health and Science University Cancer Institute and Portland Veteran’s Administration Medical Center, Portland, Oregon; the Department of Anatomical Pathology,§ University of Washington Medical Center, Seattle, Washington; the Department of Pathology and Genetic Pathology Evaluation Centre,|| Vancouver General Hospital, Vancouver, British Columbia; and the Department of Anatomic Pathology,** Cleveland Clinic Foundation, Cleveland, Ohio

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.




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