Malignancy of Gastrointestinal Stromal Tumors

Download pose: Gastrointestinal stromal tumors (GIST) are the most important mesenchymal tumors of the intestinal tract. The vast majority of GISTs exhibit activating mutations of KIT or PDGFRA, but epic alteration of GISTs is largely unknown. In this study, we aimed to clarify the involvement of DNA lation in GIST malignancy. erimental Design: A total of 106 GIST specimens were studied. Levels of LINE-1 methylation were ed using bisulfite pyrosequencing. In addition, methylation of three other repetitive sequences (Alu Yb8, te-α, and NBL2) was similarly analyzed, and CpG island hypermethylation was analyzed using MethyArray-based comparative genomic hybridization (array CGH) was carried out in 25 GIST specimens. ults: LINE-1 hypomethylation was significantly correlated with risk, and high-risk GISTs exhisignificantly lower levels of LINE-1 methylation than low-risk (61.3% versus 53.2%; P = 0.001) ermediate-risk GISTs (60.8% versus 53.2%; P = 0.002). Hypomethylation of Satellite-α and NBL2 lso observed in high-risk GISTs. By contrast, promoter hypermethylation was relatively infre(CDH1, 11.2%; MLH1, 9.8%; SFRP1, 1.2%; SFRP2, 11.0%; CHFR, 9.8%; APC, 6.1%; CDKN2A, 0%; 1A, 0%; RASSF2, 0%) and did not correlate with LINE-1 methylation or risk. Array CGH analysis ed a significant correlation between LINE-1 hypomethylation and chromosomal aberrations. clusions: Our data suggest that LINE-1 hypomethylation correlates significantly with the aggresss of GISTs and that LINE-1 methylation could be a useful marker for risk assessment. Hypomethysivene lation may increase the malignant potential of GISTs by inducing accumulation of chromosomal aberrations. Clin Cancer Res; 16(21); 5114–23. ©2010 AACR.