Comprehensive analysis of genes involved in the malignancy of gastrointestinal stromal tumors.
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.


METHODS
Using 15 cases diagnosed with GISTs, we searched for novel indicator genes by microarray analyses using an Oligo GEArray(R) 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.


CONCLUSIONS
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.
Tsumuraya
Miyako
M
Department of Surgical Oncology (Surgery I), Dokkyo Medical University, 880 Kitakobayashi Mibu-machi, Tochigi 321-0293, Japan.
Kato
Hiroyuki
H
Miyachi
Kazuhito
K
Sasaki
Kinro
K
Tsubaki
Masahiro
M
Akimoto
Kazumi
K
Sunagawa
Masakatsu
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit