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Gastrointestinal Stromal Tumor


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Free Gastrointestinal Stromal Tumor Articles


Research findings from University of Minho, Life and Health Sciences Research Institute update understanding of life sciences



2009 AUG 3 - (NewsRx.com) -- New research, 'Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs,' is the subject of a report. "Gastrointestinal stromal tumours (GISTs) are commonly driven by oncogenic mutations in KIT and PDGFRA. However, 10-40% of these patients are wild-type for these genes," researchers in Braga, Portugal report.

"The prognostic significance of wild-type GISTs is controversial, and they rarely respond to imatinib. The aim of this study was to elucidate the molecular lesions underlying wild-type GISTs tumorigenesis. Twenty-nine KIT and PDGFRA wild-type GISTs were re-assessed for the presence of 'cryptic'KIT exon 11 duplications. Using a specific polymerase chain reaction assay, three previously undetected mutations were identified. In the remaining 26 wild-type GISTs, KIT, stem cell factor (SCF), phospho-KIT and phospho-ERK expression was evaluated by immunohistochemistry. Samples were screened for gain-of-function mutations in the mitogen-activated protein kinase (MAPK) cascade. KIT and SCF co-expression associated with KIT activation was observed in approximately 30% of cases. Furthermore, phospho-ERK expression showed that MAPK is activated in approximately 30% of cases. None of RAS family (H-, K-and N-RAS) oncogenes exhibited activating mutations, whereas BRAF mutations were found in approximately 4% of cases," wrote O. Martinho and colleagues, University of Minho, Life and Health Sciences Research Institute.

The researchers concluded: "In the absence of RAS mutations, MAPK could be activated through SCF/KIT autocrine/paracrine mechanisms and/or mutated BRAF in a subset of KIT/PDGFRA wild-type GISTs."

Martinho and colleagues published their study in Histopathology (Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs. Histopathology, 2009;55(1):53-62).

For additional information, contact O. Martinho, University of Minho, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, Braga, Portugal.

Publisher contact information for the journal Histopathology is: Blackwell Publishing Inc., 350 Main St., Malden, MA 02148, USA.

Keywords: Portugal, Braga, Life Sciences, Gastrointestinal Stromal Tumor, Stem Cell Research, Gastrointestinal Stromal Tumors, Enzyme Research, Kinase, Polymerase, Diagnosis, Diagnostics, Imatinib, Antineoplastic, Protein Kinase Inhibitor, Gastroenterology, Histopathology, Pathology.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.

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