English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Gastrointestinal 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.    Methods  Seventeen 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.    Results  Of 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 .    Conclusions  The 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.

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