DNA sequence copy number changes in gastrointestinal stromal tumors: Tumorprogression and prognostic significance

To identify genetic changes related to tumor progression and find out diagn ostic and prognostic genetic markers in gastrointestinal stromal tumors (GI STs), 95 tumor samples (24 benign GISTs, 36 malignant primary GISTs, and 35 GIST-metastases) from 60 patients were studied using comparative genomic h ybridization. DNA copy number changes were detected in all samples. Benign GISTs had a mean of 2.6 aberrations/sample (losses:gains, 5:1) and signific antly fewer DNA copy number changes and fewer gains than malignant primary and metastatic GISTs (P < 0.01). High-level amplifications were not seen in benign GISTs, Malignant primary GISTs had a mean of 7.5 aberrations/tumor (losses: gains, 1.6:1), whereas the mean number of aberrations/metastatic G IST was 9 (losses:gains, 1.8:1), Frequent changes observed in all GIST grou ps included losses in chromosome arms 1p (51%), 14q (74%), and 22q (53%). G ains and high-level amplifications at 8q and 17q were significantly more fr equent in metastatic GISTs (57 and 43%) than in benign GISTs (8 and 0%; P < 0.001) and malignant primary GISTs (33 and 25%; P < 0.05). Gains and high- level amplifications at 20q were only seen in malignant primary and metasta tic GISTs (P < 0.01), and gains at 5p were not detected in benign GISTs (P < 0.01). Losses in chromosome arm 9p were never seen in benign tumors (P < 0.001), and they were more frequent in metastatic GISTs than in malignant p rimary GISTs (63 and 36%; P < 0.05). Losses in 13q were less frequent in be nign GISTs than in malignant primary (P < 0.05) and metastatic (P < 0.01) G ISTs, Our results show that several DNA copy number changes are related to the behavior of GISTs and can be used as prognostic markers for tumor progr ession.