Suppression of putative tumour suppressor gene GLTSCR2 expression in human glioblastomas

• Published in: The Journal of pathology 2008-10, Vol.216 (2), p.218-224
• Main Authors: Kim, Y.J, Cho, Y.E, Kim, Y.W, Kim, J.Y, Lee, S, Park, J.H
• Format: Article
• Language: English
• Subjects: Adult; Astrocytoma - genetics; Astrocytoma - pathology; Biological and medical sciences; Brain Neoplasms - chemistry; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Cell Line, Tumor; Chi-Square Distribution; Female; Gene Deletion; Gene Expression Regulation, Neoplastic; glioblastoma; Glioblastoma - chemistry; Glioblastoma - genetics; Glioblastoma - pathology; GLTSCR2; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Mutation; Neurology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins - analysis; Tumor Suppressor Proteins - genetics; Tumors of the nervous system. Phacomatoses; tumour suppressor gene
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2401

Glioma tumour-suppressor candidate region gene 2 (GLTSCR2/PICT-1) is localized within the well-known 1.4 Mb tumour-suppressive region of chromosome 19q, which is frequently altered in various human tumours, including diffuse gliomas. Aside from its chromosomal localization, several lines of evidence, including PTEN-phosphorylating and cell-killing activities, suggests that GLTSCR2 participates in the suppression of tumour growth and development. However, little is known about the biological functions and molecular mechanisms of GLTSCR2 as a tumour suppressor gene. We investigated the pathological significance of GLTSCR2 expression in association with the development and progression of glioblastomas, the most common malignant brain tumour. We used real-time PCR and western blot analysis to examine the expression levels of GLTSCR2 mRNA and protein in glioblastomas, normal brain tissue and in non-glial tumour tissue of different origin, and found that GLTSCR2 expression is down-regulated in glioblastomas. In addition, direct sequencing analysis and fluorescence in situ hybridization clearly demonstrates the presence of genetic alterations, such as a nonsense mutation and deletion, in the GLTSCR2 gene in glioblastomas. Finally, our immunohistochemical study demonstrates that GLTSCR2 is sequentially down-regulated according to the histological malignant progression of the astrocytic glial tumour. Taken together, our results suggest that GLTSCR2 is involved in astrocytic glioma progression. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.