High-resolution deletion mapping of chromosome 14 in stromal tumors of thegastrointestinal tract suggests two distinct tumor suppressor loci

DNA copy number losses at chromosome arm 149 are the most frequently occurr ing aberrations in gastrointestinal stromal tumors (GISTs). To characterize the deletion at 14q, we performed comparative genomic hybridization (CGH) and high-resolution deletion mapping using a panel of 32 polymorphic micros atellite markers in 30 GISTs. The GISTs were classified according to their metastatic potential and mitotic counts into 15 low-risk and 15 high-risk t umors. Losses with a minimal common overlapping region at 14q12-q24 were de tected by CGH in 16 tumors (53) (nine low-risk and seven high-risk). Invest igation with microsatellite markers was informative in 690 analyses (72%). Loss of heterozygosity (LOH) with at least one marker was detected in 279 a nalyses in 24 tumors (80%). Deletions were equally frequent in low-risk and high-risk GISTs. Two common deletion regions were identified at 14q11.1-q1 2 and 14q23-q24.3. The highest frequencies of deletions were seen in region s corresponding to markers D14S283 (20/28, 71%) at 14q11.1-q12 and D14S258 (17/27, 63%) at 14q23-q24, suggesting that these are two tumor suppressor l oci. (C) 2000 Wiley-Liss, Inc.