DNA copy number changes in gastrointestinal stromal tumors - A distinct genetic entity

It is not universally agreed whether gastrointestinal stromal tumors (GISTs ) are phenotypical variants of leiomyomas (LM) and leiomyosarcomas (LMS), o r whether they belong to a separate phenotypic entity with a different gene tic background. This is a summary of our published results from comparative genomic hybridization studies performed in order to solve this question. W e studied DNA copy number changes in 32 immunohistochemically well-defined GISTs (13 malignant, 3 borderline, and 16 benign tumors), 14 LM, and 29 LMS . In GISTs, a consistent finding was the loss of DNA copy numbers in chromo some 14q. This loss was detected in 75 % of the benign tumors, in 62 % of t he malignant tumors, and in two out of the three borderline tumors with the minimal overlapping region located to 14q22. The loss was not seen in LM a nd in LMS it was rare (4 cases, 13 %). Only three LM cases showed DNA copy number changes: gains in chromosome 3, 4, 5, 8, and 17. A total of 137 loss es and 204 gains were detected in LMS. The most frequent losses were detect ed in 10q (20 cases, 69 %) and 13q (17 cases, 59 %). The most frequent gain s were detected in 17p (16 cases, 55 %). The most frequent high-level ampli fications were detected in 17p (7 cases, 24 %) and 8q (6 cases, 21 %). Our results indicate that DNA copy number losses in 14q are an early change during the oncogenesis of GISTs. Moreover, the pattern of the demonstrated DNA copy number changes suggests that GISTs are a phenotypic and genetic e ntity separate from leiomyomas and leiomyosarcomas.