GIST: particular aspects related to cell cultures, xenografts, and cytogenetics

In less than half a decade, gastrointestinal stromal tumors (GIST) have emerged from historical anonymity to become a model of kinase-targeted therapies. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT or PDGFRA tyrosine kinase genes, and such mutations have predictive and prognostic value. In this regard, the in vitro and in vivo models have provided valuable tools for understanding the molecular pathology of this interesting neoplasm. This review charts particular aspects in the field of cell cultures and tumor xenografts in nude mice in GIST and their implication in the establishment of appropriate models for discovering and testing therapy. The cytogenetic features of these tumors are also discussed. Classic karyotyping, loss of heterozygosity, fluorescent in situ hybridization, comparative genomic hybridization (CGH), and CGH-array analyses have shown that chromosomal numerical abnormalities and loss of genetic material at chromosomes 1p, 9p, 14q, and 22q are significantly associated with GIST malignancy and response to treatment. Furthermore, these regions constitute "hot" areas for finding candidate genes involved in the pathogenesis of GISTs. A deeper knowledge of these genetic aspects of GIST will provide a better understanding of this neoplasm that could translate into clinical practice.