PT - JOURNAL ARTICLE AU - TSUMURAYA, MIYAKO AU - KATO, HIROYUKI AU - MIYACHI, KAZUHITO AU - SASAKI, KINRO AU - TSUBAKI, MASAHIRO AU - AKIMOTO, KAZUMI AU - SUNAGAWA, MASAKATSU TI - Comprehensive Analysis of Genes Involved in the Malignancy of Gastrointestinal Stromal Tumors DP - 2010 Jul 01 TA - Anticancer Research PG - 2705--2715 VI - 30 IP - 7 4099 - http://ar.iiarjournals.org/content/30/7/2705.short 4100 - http://ar.iiarjournals.org/content/30/7/2705.full SO - Anticancer Res2010 Jul 01; 30 AB - Background: During tumorigenesis of gastrointestinal stromal tumors (GISTs), the most frequent changes are reported to be gain-of-function mutations in the C-KIT proto-oncogene. However, we speculated that additional genetic alterations are required for the progression of GISTs. Patients and Methods: Using 15 cases diagnosed with GISTs, we searched for novel indicator genes by microarray analyses using an Oligo GEArray® PI3K-AKT Signaling Pathway Microarray Kit. In addition, we analyzed the mutational status of C-KIT and the proliferation status indicated by the Ki-67 index. Results: The tumor localizations of the 15 GISTs were as follows: 8 in the stomach; 2 in the small intestine; 2 in the mesentery; 1 in the duodenum; 1 in the rectum; and 1 in liver. Regarding the C-KIT gene analysis, mutations in exon 11 were detected in 11 out of 13 patients. In 1 out of the 13 patients, mutations were detected in both exons 11 and 13. No genetic abnormalities were identified in 1 patient. The Ki-67 labeling indices were significantly lower for the low-risk and intermediate-risk groups than for the high-risk group (p=0.0440). No specific genes were overexpressed in the >1% Ki-67 group. Regarding the primary lesion sites, the following 6 genes were overexpressed in tumors in the stomach: RBL2, RHOA, SHC1, HSP90AB1, ACTB and BAS2C. Conclusion: Gene analysis is currently only useful for diagnostic assessment and predicting therapeutic effects. However, it may be possible for new malignancy-related factors to be identified by comparing and investigating gene expression levels and other factors using such analyses.