CITED4 as prognostic marker in oligodendroglial tumors
Reference Number TO 09-0021
The Challenge
Cancer of the central nervous system (CNS), is a complex disease and still represents a leading cause of death in the world. The prognosis for most patients with cancer of the CNS, particular with brain tumours, remains poor. The establishment of tumor grade is a key determinant in the choice of a therapeutic approach and in prognosis. Presently there are no tumor markers available that are useful for diagnosis of CNS tumors including oligodendroglial tumors.
The technology
Loss of heterozygosity (LOH) on chromosome arms 1p and 19q is frequent in oligodendroglial tumors and associated with sensitivity to radio- and chemotherapy as well as favorable prognosis. Researchers at the German Cancer Research Center (DKFZ) found that oligodendroglial tumors with LOH 1p/19q showed significantly lower expression of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminaldomain 4 gene (CITED4) at 1p34.2 as compared to gliomas without LOH 1p/19q. Mutational analysis showed no mutations in the CITED4 coding sequence. However, LOH 1p/19q and low expression of CITED4 transcripts were closely associated with hypermethylation of the CITED4 promoter. Treatment of CITED4 hypermethylated glioma cells with 5-aza-2’-deoxycytidine and trichostatine A markedly increased CITED4 expression. Furthermore, CITED4 hypermethylation was a significant predictor of longer survival in patients with oligodendroglial tumors. Taken together, the results suggest CITED4 as a putative tumor suppressor gene that is epigenetically silenced in the majority of oligodendroglial tumors with LOH 1p/19q and represents a powerful prognostic marker.
Commercial Use
In-licensing/Cooperation opportunity for the development of diagnostic tools and therapeutics in the field of oligodendroglial tumors.
Patent situation
An European priority patent application is pending.
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