The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status

Robert B. West, Christopher Corless, Xin Chen, Brian P. Rubin, Subbaya Subramanian, Kelli Montgomery, Shirley Zhu, Catherine A. Ball, Torsten O. Nielsen, Rajiv Patel, John R. Goldblum, Patrick O. Brown, Michael Heinrich, Matt Van De Rijn

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalAmerican Journal of Pathology
Volume165
Issue number1
StatePublished - Jul 2004

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Gastrointestinal Stromal Tumors
Mutation
Neoplasms
Aggressive Fibromatosis
Fibroma
Neurilemmoma
Oligonucleotide Array Sequence Analysis
Protein-Tyrosine Kinases
In Situ Hybridization
Immune Sera
Proteins
Differential Diagnosis
Rabbits
Gene Expression
Antigens
Peptides

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

West, R. B., Corless, C., Chen, X., Rubin, B. P., Subramanian, S., Montgomery, K., ... Van De Rijn, M. (2004). The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. American Journal of Pathology, 165(1), 107-113.

The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. / West, Robert B.; Corless, Christopher; Chen, Xin; Rubin, Brian P.; Subramanian, Subbaya; Montgomery, Kelli; Zhu, Shirley; Ball, Catherine A.; Nielsen, Torsten O.; Patel, Rajiv; Goldblum, John R.; Brown, Patrick O.; Heinrich, Michael; Van De Rijn, Matt.

In: American Journal of Pathology, Vol. 165, No. 1, 07.2004, p. 107-113.

Research output: Contribution to journalArticle

West, RB, Corless, C, Chen, X, Rubin, BP, Subramanian, S, Montgomery, K, Zhu, S, Ball, CA, Nielsen, TO, Patel, R, Goldblum, JR, Brown, PO, Heinrich, M & Van De Rijn, M 2004, 'The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status', American Journal of Pathology, vol. 165, no. 1, pp. 107-113.
West, Robert B. ; Corless, Christopher ; Chen, Xin ; Rubin, Brian P. ; Subramanian, Subbaya ; Montgomery, Kelli ; Zhu, Shirley ; Ball, Catherine A. ; Nielsen, Torsten O. ; Patel, Rajiv ; Goldblum, John R. ; Brown, Patrick O. ; Heinrich, Michael ; Van De Rijn, Matt. / The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. In: American Journal of Pathology. 2004 ; Vol. 165, No. 1. pp. 107-113.
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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.",
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