Establishment and characterisation of GEMM of GIST

Gastrointestinal stromal tumour(GIST) is a tumour of mesenchymal origin and accounts for the majority of mesenchymal tumour of gastrointestinal tract. Its incidence is evaluated between 7 to 15 cases per 1 million persons per year. The most common mutation in GIST is the gain-of-function mutation of the KIT and gain-of-function mutation of the platelet-derived growth factor (PDGF) receptor alpha (PDGFRA). The relative frequency of KIT mutation is around 80% whereas the relative frequency of PDGFRA is between 5-8%. However, around 12-15% of GIST tumours are both KIT and PDGFRA wild-type. There is a high need to better understand the molecular drivers for GIST tumours in general and KIT and PDGFRA wild-type GIST tumours in particular. In order to better understand, KIT and PDGFRA wild-type GIST, we aim to produce a genetically engineered mouse model of GIST driven by BRAF and PI3K mutations. To do so, we have crossed mice expressing a tamoxifen dependent Cre-recombinase ERT2 under a glial-cell specific promoter (Glial fibrillary acidic protein or GFAP) with BrafCA/CA;Pik3caLat/Lat. The resulting mice when injected with tamoxifen give rise to GIST in mice. Our aim is now to better understand and characterise the development of GIST in this model.

Saurav Subedi