Three Cases of Canine Gastrointestinal Stromal Tumors with Multiple Differentiations and c-kit-Expression

Kumagai, Kazuyoshi; Uchida, Katsuhisa; Miyamoto, Toru; Ushigusa, Takahiro; Shinohara, Syusaku; Yamaguchi, Ryoji; Tateyama, Susumu

doi:10.1292/jvms.65.1119

Cited by 15 publications

(19 citation statements)

References 20 publications

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“…The most interesting histological finding and, to our knowledge, the first report in humans, was the presence of multinuclear giant cells in 92% of PDGFRα‐mutated GISTs in our series. In only one previous study were giant cells described within a canine GIST, but the mutational status of this tumour was not determined 15 . In contrast to PDGFRα‐mutated GISTs, the majority of c‐kit‐mutated and wt‐GISTs exhibited a spindle cell phenotype.…”

Section: Discussionmentioning

confidence: 95%

PDGFRα‐ and c‐kit‐mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features

et al. 2005

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Features of PDGFRalpha-mutated GISTs are multinuclear giant cells and dot-like staining for PDGFRalpha. In contrast, c-kit-mutated GISTs display a spindle cell phenotype and Kit-dots on immunohistochemistry. Our findings not only help to distinguish distinctive entities of GISTs using histological and immunhistochemical features, but also indicate that Kit and PDGFRalpha are differentially regulated in a subset of GISTs.

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Section: Discussionmentioning

confidence: 95%

PDGFRα‐ and c‐kit‐mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features

et al. 2005

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“…TPX2 activity outside the nucleus, just like in vitro ( Figure 6B), is likely to cause microtubule polymerization, which is essential for prospindle assembly. Prospindle accumulation of TPX2 coincides with the AURORA2 and g-tubulin localizations (Liu et al, 1993;Kumagai et al, 2003;Kawabe et al, 2005). During prometaphase, At TPX2 associated with the spindle microtubules.…”

Section: Discussionmentioning

confidence: 99%

The Plant TPX2 Protein Regulates Prospindle Assembly before Nuclear Envelope Breakdown

et al. 2008

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The Targeting Protein for Xklp2 (TPX2) is a central regulator of spindle assembly in vertebrate cells. The absence or excess of TPX2 inhibits spindle formation. We have defined a TPX2 signature motif that is present once in vertebrate sequences but twice in plants. Plant TPX2 is predominantly nuclear during interphase and is actively exported before nuclear envelope breakdown to initiate prospindle assembly. It localizes to the spindle microtubules but not to the interdigitating polar microtubules during anaphase or to the phragmoplast as it is rapidly degraded during telophase. We characterized the Arabidopsis thaliana TPX2-targeting domains and show that the protein is able to rescue microtubule assembly in TPX2-depleted Xenopus laevis egg extracts. Injection of antibodies to TPX2 into living plant cells inhibits the onset of mitosis. These results demonstrate that plant TPX2 already functions before nuclear envelope breakdown. Thus, plants have adapted nuclear-cytoplasmic shuttling of TPX2 to maintain proper spindle assembly without centrosomes.

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“…Gastrointestinal stromal tumors occur in many species including humans, dogs [1-3], and horses [4,5]. GISTs can metastasize to the liver and peritoneal cavity, warranting a very poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

et al. 2010

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BackgroundGastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of c-KIT in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), all of which have been implicated in human GISTs.MethodsSeventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples.ResultsOf these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA.ConclusionsThe deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further demonstrates that spontaneously occurring canine GISTs share molecular features with human GISTs and are an appropriate model for human GISTs.

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Three Cases of Canine Gastrointestinal Stromal Tumors with Multiple Differentiations and c-kit-Expression

Cited by 15 publications

References 20 publications

PDGFRα‐ and c‐kit‐mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features

PDGFRα‐ and c‐kit‐mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features

The Plant TPX2 Protein Regulates Prospindle Assembly before Nuclear Envelope Breakdown

Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

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