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Initial clinical features and histopathology often fail to distinguish between benign and malignant gastrointestinal stromal tumours (GISTs). These tumours probably originate in the intestinal stem cells of Cajal and it is not possible to compare gene expression profiles of the malignant tumours and the normal stem cells. Researchers in Virginia, USA have compared benign with malignant tumours.
They studied 25 GISTs, all c-KIT-positive on immunohistochemistry and with GIST histology. At diagnosis they were classified as benign (8), malignant (11), or uncertain (6). In gene array analyses performed on the first nine tumours (3 benign, 6 malignant) the expression of 1174 genes was evaluated for each sample. Compared with benign GISTs, malignant GISTs showed overexpression of 27 genes of which eight were overexpressed in five or more of the six malignant tumours. The eight genes were VIL2, COL8A1, CCNB1, HMG2, TSG101 tumour susceptibility protein, CENP-F kinetochore protein, protein tyrosine kinase 2 (FAK), and protein kinase DYRK2. Quantitative real time RT-PCR confirmed these findings. When the additional 16 tumours were assessed using quantitative real time RT-PCR the five malignant tumours showed similar gene overexpression. Three of the six patients whose tumours were originally classified as of uncertain malignant potential died of the disease and their tumours segregated with the other malignant tumours as regards gene expression. The tumours of the three patients in this group who had no evidence of malignancy on follow up showed the benign gene expression profile. The six genes most significantly overexpressed in malignant tumours were VIL2, CCNB1, HMG2, TSG101, CENP-F, and FAK. The two gene pairs most significantly overexpressed in malignant tumours were CCNB1-CENP-F and CCNB1-FAK.
These findings help in understanding the oncogenesis of GISTs and provide a means of distinguishing between benign and malignant tumours.