Clinical Characterization and Mutations of the c-kit Gene in Dogs with Gastrointestinal Stromal Tumors

Abstract

Summary:We studied the clinical characteristics of 11 dogs with gastrointestinal stromal tumors and investigated the c-kit gene mutations in the resected tumor tissues. The affected dogs were aged 6 to 14 years, and there were six males and five females. The tumors originated in the cecum in seven cases (63.6%), the small intestine in two cases (18%), and the duodenum and the colon in one case each (both 9%). The type of cancerous growth was classified as extra-luminal in seven cases (63.6%), intra-mural in one case (9%), intra-luminal in two cases (18%), and indistinct in one case (9%). C-kit gene mutations were found in exon 11 in six cases (54.5%), while there were none in exons 8, 9 and 13. C-kit gene mutations occurred in 54.5% of cases and in 80% of the cases involving the cecum and extra-luminal growth; hence, c-kit gene mutation might be related to the cause of canine gastrointestinal stromal tumors.

Gastrointestinal stromal tumors with Kit gene mutation in 4 guinea pigs (Cavia porcellus)

“…22 Contrarily, the large intestine (particularly the cecum) is the most common location in dogs, followed by the small intestine and stomach. 6,8 In this study, GISTs were most common in the stomach, similar to those in humans. The growth patterns of GISTs can be extraluminal (abluminal expansion from the gastrointestinal wall), intramural (expansion within the gastrointestinal wall), or intraluminal (protrusion into the gastrointestinal lumen), with the extraluminal pattern being the most common in humans (79%) and dogs (70%).…”

“…The growth patterns of GISTs can be extraluminal (abluminal expansion from the gastrointestinal wall), intramural (expansion within the gastrointestinal wall), or intraluminal (protrusion into the gastrointestinal lumen), with the extraluminal pattern being the most common in humans (79%) and dogs (70%). 6,8,22 All of these guinea pig tumors had an extraluminal growth pattern. GIST metastasis occurs in 23% of humans 22 and 29%-45% of dogs 6,4 .…”

“…Gain-of-function mutations in Kit exon 11 are frequently found in human and canine GISTs. 6,10,22,27 We aimed to describe the clinical presentation, pathologic findings, and presence of Kit mutations of GISTs in guinea pigs.…”

“…Few studies have reported its use in other animals, such as chimpanzees, horses, pigs, cats, and guinea pigs. 6,8,12,17,[20][21][22][23][24][25][26][27]31 Some reports of GISTs in horses and monkeys have not been confirmed by immunohistochemistry. 1,4,11 The anatomic location of GISTs varies according to the species, with the stomach and small intestine and the cecum and small intestine being the most common locations in humans and dogs, respectively.…”

“…1,4,11 The anatomic location of GISTs varies according to the species, with the stomach and small intestine and the cecum and small intestine being the most common locations in humans and dogs, respectively. 6,8,22 Some human GISTs do not express KIT antigens. Discovered-on-GIST 1 (DOG1) encodes a calcium-activated chloride channel in the interstitial cells of Cajal, and immunohistochemistry for DOG1 is more sensitive and specific than anti-KIT for GIST diagnosis in humans.…”