KIAA0510, the 3'-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas.

ABSTRACT

AIMS: Studying the molecules and signalling pathways regulating glioma invasiveness is a major challenge because these processes determine malignancy, progression, relapse and prognosis. We took advantage of our previous study focused on genes that were critical in tumour invasion to further study here an unknown sequence, referred to as KIAA0510, the chromosomal location of which was 1q25, described as a 5596-bp long mRNA and that we found to be significantly overexpressed in pilocytic astrocytomas compared with glioblastomas. METHODS AND RESULTS: Using in silico analysis as well as Polymerase chain reaction techniques, we decipher the full genomic characterization of the KIAA0510 sequence and demonstrate that KIAA0510 constitutes the 3'-untranslated region of tenascin-R gene. We have clearly confirmed the overexpression of tenascin-R in pilocytic astrocytomas vs. glioblastomas at mRNA and protein levels. We also analysed a large series of various brain tumours and found that in the group of astrocytic tumours, tenascin-R expression decreased with malignancy, whereas oligodendrogliomas sometimes retained a high level of tenascin-R even in high-grade tumours. Gangliogliomas strongly expressed tenascin-R too. In contrast, ependymomas and meningiomas were negative. In normal brain, tenascin-R was exclusively expressed by normal oligodendrocytes and subsets of neurones during post-natal development and in adulthood, where it could differentially affect cellular adhesiveness and/or differentiation. CONCLUSION: KIAA0510, the 3'-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas. Gangliogliomas shared with pilocytic astrocytomas strong tenascin-R expression. Whether tenascin-R overexpression negatively influences brain invasion remains to be determined.