Abstract

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. Formerly GISTs were commonly classified histologically as leiomyosarcomas; however, they are now known to arise from the interstitial cells of Cajal. Majority of GISTs overexpress KIT and have characteristic mutations within the gene, which are the targets of drug treatment with tyrosine kinase inhibitors. Leiomyosarcoma is a malignant tumour of smooth muscle differentiation and falls into a group of sarcomas that show complex karyotypic changes with no consistent recurrent genetic abnormality. We have used comparative genomic hybridization in combination with fluorescence in situ hybridization to determine genetic differences between the tumour types. We found leiomyosarcomas and GISTs share common regions of chromosomal 13q and 11q imbalance, in addition to more specific 1p and 8p losses in leiomyosarcoma and 15q and 22q losses in GISTs. More importantly, we have shown for the first time a deletion in the ataxia telangiectasia mutated (ATM) gene locus with decreased/absent expression of ATM protein, and amplification in the region 13q21-q32 in both tumour types, suggesting both regions may play a role in leiomyosarcoma and GIST biology.