Article
Methylation-specific MLPA as a technique for detection of inactivated tumour supressor genes in intracranial neoplasms
Methylierungsspezifische MLPA als Technik zum Nachweis inaktivierter Tumorsuppressorgene in intrakraniellen Tumoren
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Published: | April 11, 2007 |
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Outline
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Objective: Inactivation of tumour suppressor genes (TSGs) has been detected in several cerebral tumours during the last years with some of them becoming more and more relevant for special treatment like the 1p/19Q loss in oligodendrogliomas or the inactivation of the MGMT gene in glioblastomas. Here we describe our experience with methylation specific multiplex ligation-dependent probe amplification as a relatively simple approach to detect inactivated TSGs in clinical specimens.
Methods: We analysed promotor methylation and deletion/amplification status of 41 tumour suppressor genes in a series of 29 intracranial tumours of different biological behaviour (15 meningeomas, seven gliomas and seven metastases of extracranial tumours) and compared the data with the histolological and clinical findings; we discuss the results against current literature.
Results: The most frequent events in meningiomas were deletion of 22q (9/15), of 12q (10/15), of 11q (11/15) and of 3p (12/15). This confirms previous findings (e.g. 22q) but also suggests novel frequently affected regions (e.g. 12q). The number of deletions tended to be higher in more aggressive tumours like grade III meningeomas, glioblastomas of metastases. Methylation was generally rare except in the promoter region of the RASSF 1 gene (five of seven gliomas and five of seven metastases).
Conclusions: The technique seems to be a valid and simple method to detect genetical aberrations such as promoter hypermethylation, deletion and amplification in intracranial tumour tissue. Further investigation will follow especially concerning the MGMT – gene in glioblastoma and the detection of possible tumour progression events in meningeomas.