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[Cancer Research 60, 3899-3903, July 15, 2000]
© 2000 American Association for Cancer Research

Tumor Biology

DNA Sequence Copy Number Changes in Gastrointestinal Stromal Tumors: Tumor Progression and Prognostic Significance1

Wa’el El-Rifai, Maarit Sarlomo-Rikala, Leif C. Andersson, Sakari Knuutila2 and Markku Miettinen

Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki [W. E-R., S. K.], Department of Pathology, Haartman Institute, University of Helsinki [M. S-R., L. C. A.], FIN-00029 HUCH Helsinki, Finland; Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000 [M. M.]; and Department of Human Genetics, National Research Center, Cairo, Egypt [W. E-R.]

To identify genetic changes related to tumor progression and find out diagnostic and prognostic genetic markers in gastrointestinal stromal tumors (GISTs), 95 tumor samples (24 benign GISTs, 36 malignant primary GISTs, and 35 GIST-metastases) from 60 patients were studied using comparative genomic hybridization. DNA copy number changes were detected in all samples. Benign GISTs had a mean of 2.6 aberrations/sample (losses:gains, 5:1) and significantly 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 GIST was 9 (losses:gains, 1.8:1). Frequent changes observed in all GIST groups included losses in chromosome arms 1p (51%), 14q (74%), and 22q (53%). Gains and high-level amplifications at 8q and 17q were significantly more frequent 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 metastatic 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 primary GISTs (63 and 36%; P < 0.05). Losses in 13q were less frequent in benign GISTs than in malignant primary (P < 0.05) and metastatic (P < 0.01) GISTs. 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 progression.




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