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Background  A  KIT  gain of function mutation is present in 70% of gastrointestinal stromal tumors (GISTs) and the wild-type (WT) allele is deleted in 5 to 15% of these cases. The WT  KIT  is probably deleted during GIST progression. We aimed to identify the mechanism of WT  KIT  loss and to determine whether other genes are involved or affected.    Methods  Whole-genome SNP array analyses were performed in 22 GISTs with  KIT  exon 11 mutations, including 11 with WT loss, to investigate the mechanisms of WT allele deletion. CGH arrays and FISH were performed in some cases. Common genetic events were identified by SNP data analysis. The 9p21.3 locus was studied by multiplex quantification of genomic DNA.    Results  Chromosome instability involving the whole chromosome/chromosome arm (whole C/CA) was detected in 21/22 cases. The GISTs segregated in two groups based on their chromosome number: polyGISTs had numerous whole C/CA gains (mean 23, range [9 to 43]/3.11 [1 to 5]), whereas biGISTs had fewer aberrations. Whole C/CA losses were also frequent and found in both groups. There were numerous copy-neutral losses of heterozygosity (cnLOH) of whole C/CA in both polyGIST (7/9) and biGIST (9/13) groups. cnLOH were frequent on 4q, 11p, 11q, 1p, 2q, 3p and 10, and never involved 12p, 12q, 20p, 20q or 19q. Other genetic alterations included segmental chromosome abnormalities, complete bi-allelic deletions (homozygous deletions) and, more rarely, amplifications. Nine of 11 GISTs with homozygous  KIT  exon 11 mutations had cnLOH of chromosome 4.    Conclusion  The cnLOH of whole C/CA is a frequent genetic alteration in GISTs and is closely associated with homozygous mutations of  KIT  and WT allele deletion.    Electronic supplementary material  The online version of this article (doi:10.1186/1476-4598-13-246) contains supplementary material, which is available to authorized users.

Copy-neutral loss of heterozygosity and chromosome gains and losses are frequent in gastrointestinal stromal tumors