MicroRNA expression profile of gastrointestinal stromal tumors is distinguished by 14q loss and anatomic site.
MicroRNAs are known to regulate gene expression. Although unique microRNA expression profiles have been reported in several tumors, little is known about microRNA expression profiles in GISTs. To evaluate the relationship between microRNA expression and clinicopathologic findings of GISTs, we analyzed the microRNA expression profiles of GISTs. We used fresh frozen tissues from 20 GISTs and analyzed KIT and PDGFRA mutations and chromosomal loss status. MicroRNA expression was analyzed using a microRNA chip containing 470 microRNAs. Using unsupervised hierarchical clustering analysis, we found four distinct microRNA expression patterns in our 20 GISTs. Six GISTs that did not have 14q loss formed a separate cluster. In the 14 GISTs with 14q loss, 5 small bowel GISTs formed a separate cluster and the remaining 9 GISTs could be divided into two groups according to frequent chromosomal losses and tumor risk. We found 73 microRNAs that were significantly down-regulated in the GISTs with 14q loss; 38 of these microRNAs are encoded on 14q. We also found many microRNAs that were down-regulated in small bowel and high-risk group GISTs. Most of the microRNAs down-regulated in the high-risk group and small bowel GISTs are known to be involved in tumor progression, specifically by stimulating mitogen-activated protein kinase (MAPK) and the cell cycle. The microRNA expression patterns of GISTs are closely related to the status of 14q loss, anatomic site, and tumor risk. These findings suggest that microRNA expression patterns can differentiate several subsets of GISTs.
Choi
Hee-Jung
HJ
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Lee
Hanna
H
Kim
Hyunki
H
Kwon
Ji Eun
JE
Kang
Hyun Ju
HJ
You
Kwon Tae
KT
Rhee
Hwanseok
H
Noh
Sung Hoon
SH
Paik
Young-Ki
YK
Hyung
Woo Jin
WJ
Kim
Hoguen
H
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha