Molecular characterization of PDGFR-alpha/PDGF-A and c-KIT/SCF in gliosarcomas

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Reis, RM (Author) Other; Martins, A (Author) Other; Ribeiro, SA (Author) Other; Basto, D (Author) Other; Longatto, A (Author) Other; Schmitt, FC (Author) FMUP; Lopes, JM (Author) FMUP

Journal

The Journal is awaiting validation by the Administrative Services.

Title: CELLULAR ONCOLOGY

Vol. 27

Pages: 319-326

ISSN: 1570-5870

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 26 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-000-5AG

DOI: 10.1155/2005/347863

Abstract (EN): Gliosarcomas are rare and poorly characterized malignant brain tumors that exhibit a biphasic tissue pattern with areas of gliomatous and sarcomatous differentiation. These tumors are histological variants of glioblastoma, displaying a similar genetic profile and dismal prognosis. Up-regulation of PDGFR subfamily of tyrosine kinase members, PDGFR-a and c-Kit, and their intracellular effectors RAS/RAF/MAPK has a crucial role in the cancer development. In addition, signal transduction mediated by activating mutations of c-Kit and PDGFR can be effectively blocked by specific tyrosine kinase inhibitors, such as Imatinib mesylate. The aim of this study was to characterize the molecular alterations of PDGFR signaling in gliosarcomas. Six cases were analyzed by immunohistochemistry for the expression of PDGFR-alpha, c-Kit and their ligands PDGF-A and SCF, respectively. The cases were further evaluated for the presence of activating mutations of PDGFR-alpha (exons 12 and 18) and c-kit (exons 9, 11, 13, and 17), as well as B-RAF (exons I I and 15). Expression of PDGF-A was found in all cases and co-expression of PDGFR-a was observed in three cases. Four cases showed expression of SCF, and c-Kit was observed only in one case that also expressed SCE Generally, immunoreaction predominates in the glial component. The mutational analysis of PDGFR-alpha showed the presence of an IVS17-50insT intronic insertion in two cases, one of them also with a 2472C > T silent mutation; this silent mutation was also found in another case. Glioma cell line analysis of IVS17-50insT insertion showed no influence on PDGFR-a gene splicing. No mutations were detected in c-kit and B-RAF oncogenes. Our results indicate that activating mutations of PDGFR-a, c-kit and B-RAF are absent in gliosarcomas. Nevertheless, the presence of a PDGFR-a/PDGFA and c-Kit/SCF autocrine/paracrine stimulation loop in a proportion of cases, supports the potential role of specific tyrosine kinase inhibitors in the treatment of gliosarcomas.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8