Gastrointestinal Stromal Tumours (GISTs) with KRAS Mutation: A Rare but Important Subset of GISTs

Dorinda Mullen; Rajkumar Vajpeyi; Jose-Mario Capo-Chichi; Klaudia Nowak; Newton Wong; Runjan Chetty

doi:10.1155/2023/4248128

Gastrointestinal Stromal Tumours (GISTs) with KRAS Mutation: A Rare but Important Subset of GISTs

Case Rep Gastrointest Med. 2023 Aug 24:2023:4248128. doi: 10.1155/2023/4248128. eCollection 2023.

Authors

Dorinda Mullen¹, Rajkumar Vajpeyi¹, Jose-Mario Capo-Chichi², Klaudia Nowak¹, Newton Wong³, Runjan Chetty⁴

Affiliations

¹ Division of Anatomical Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Canada.
² Department of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, ON, Canada.
³ Department of Cellular Pathology, Southmead Hospital, Bristol, UK.
⁴ Deciphex, Dublin, Ireland.

Abstract

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the GI tract, usually found in the stomach, jejunum, and ileum. Typically, they are KIT or PDGFR-mutated, allowing for targetable treatments with tyrosine kinase inhibitors such as imatinib. Here, we present two KRAS-mutated wild-type gastrointestinal tumours (GISTs). Both cases occurred in the small bowel of females. Immunohistochemical studies on both tumours showed KIT and DOG-1 positivity, with SDHB retained. Molecular analysis revealed a KRAS G12D mutation and a KRAS G13D mutation, respectively. Wild-type GISTs are extremely uncommon. They typically occur in the stomach or the small bowel. KRAS is one of the genes implicated in this subset of GIST, with KRAS G12D being the most frequently encountered mutation. GIST KRAS mutations can arise alone or in conjunction with KIT, PDFRA, or BRAF mutations. Identification of these rare molecular subtypes is clinically important due to their resistance to imatinib therapy.

Publication types

Case Reports