Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors.

Purpose: Previous studies have reported clinical correlates for KIT mutations in GISTs, but in most of those studies the KIT mutations were found in less than 50% of the GISTs. The aim of this study was to evaluate the prognostic relevance for KIT mutations in a series of GISTs in which the mutations were evaluated intensively by genomic and cDNA sequencing.

Patients And Methods: A comprehensive clinical and pathologic analysis of 48 patients with GISTs who had snap-frozen tissue was performed.

Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.

Background: Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors.

Methods: We conducted an open-label, randomized, multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor.

Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations.

Recent studies have done much to reveal the biological and genetic underpinnings of gastrointestinal stromal tumors (GISTs). Constitutive activation of the KIT receptor tyrosine kinase is a central pathogenetic event in most GISTs and generally results from oncogenic point mutations which can involve either extracellular or cytoplasmic domains of the receptor. Oncogenic mutations enable the KIT receptor to phosphorylate various substrate proteins, leading to activation of signal transduction cascades which regulate cell proliferation, apoptosis, chemotaxis, and adhesion.

Peripheral nerve sheath tumors from patients with neurofibromatosis type 1 do not have the chromosomal translocation t(X;18).

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder that is caused by a mutation in the NF1 gene. Hallmark characteristics include dermal neurofibromas, café-au-lait spots, and learning disabilities. In approximately 25% of NF1 cases, plexiform neurofibromas, or peripheral nerve sheath tumors (PNSTs) that involve large segments of nerve sheath and nerve root, can form, of which a small percentage become malignant (MPNST).

Molecular Insights into the Histogenesis and Pathogenesis of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) have long been problematic in terms of classification and determination of prognosis. Recent studies have suggested that GISTs differentiate toward a phenotype resembling the interstitial cells of Cajal. This has led to the important discovery that activating mutations in the KIT receptor tyrosine kinase play an important role in the pathogenesis of GISTs.