BACKGROUND: DOG1 is a novel gene on gastrointestinal stromal tumors (GISTs) that encodes the chloride channel protein anoctamin 1, also known as discovered on GIST-1 (DOG1) protein. DOG1 antibodies are a sensitive and specific marker against GIST positive for CD117 and CD34 and negative for CD117 and CD34. DOG1 is also independent of KIT or PDGFRA mutation status and considered specific for GIST when it was first discovered in 2004. METHODS: The previous 10 years of literature was searched for articles relating to DOG1. We critically reviewed 12 studies that showed DOG1 was positive in 250 cases of 2,360 tested non-GIST neoplasms (10.6%) at different anatomical sites using monoclonal, polyclonal, or nonspecified antibodies. Criteria for positivity varied between the studies. RESULTS: Monoclonal and polyclonal DOG1 antibodies were reactive in various different non-GIST tumor types spanning 9 organ systems in addition to normal salivary and pancreatic tissues. The tumors included were renal oncocytoma (100%), renal cell carcinoma chromophobe type (86%), solid pseudopapillary neoplasm of the pancreas (51%), neoplastic salivary tissue (17%), synovial sarcoma (15%), leiomyoma (10%), pancreatic adenocarcinoma (7%), and leiomyosarcoma (4%). CONCLUSIONS: By contrast to the original concept that DOG1 antibodies are specific to GIST neoplasms, the studies reviewed showed that the data suggest DOG1 positivity in select non-GIST tumors. Only in the appropriate clinical and pathological context is DOG1 positivity specific and helpful in the diagnosis of GIST.
BACKGROUND:DOG1 is a novel gene on gastrointestinal stromal tumors (GISTs) that encodes the chloride channel protein anoctamin 1, also known as discovered on GIST-1 (DOG1) protein. DOG1 antibodies are a sensitive and specific marker against GIST positive for CD117 and CD34 and negative for CD117 and CD34. DOG1 is also independent of KIT or PDGFRA mutation status and considered specific for GIST when it was first discovered in 2004. METHODS: The previous 10 years of literature was searched for articles relating to DOG1. We critically reviewed 12 studies that showed DOG1 was positive in 250 cases of 2,360 tested non-GIST neoplasms (10.6%) at different anatomical sites using monoclonal, polyclonal, or nonspecified antibodies. Criteria for positivity varied between the studies. RESULTS: Monoclonal and polyclonal DOG1 antibodies were reactive in various different non-GIST tumor types spanning 9 organ systems in addition to normal salivary and pancreatic tissues. The tumors included were renal oncocytoma (100%), renal cell carcinoma chromophobe type (86%), solid pseudopapillary neoplasm of the pancreas (51%), neoplastic salivary tissue (17%), synovial sarcoma (15%), leiomyoma (10%), pancreatic adenocarcinoma (7%), and leiomyosarcoma (4%). CONCLUSIONS: By contrast to the original concept that DOG1 antibodies are specific to GIST neoplasms, the studies reviewed showed that the data suggest DOG1 positivity in select non-GIST tumors. Only in the appropriate clinical and pathological context is DOG1 positivity specific and helpful in the diagnosis of GIST.
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