[Different hypermethylation status of RASSF1A in medulloblastoma and supratentorial primitive neuroectodermal tumor].
OBJECTIVE
To investigate the epigenetic involvement of RASSF1A in intracranial primitive neuroectodermal tumors (PNETs) and compare the methylation patterns between medulloblastoma (MBs) and supratentorial PNETs (SPNETs).


METHODS
The methylation status at the promoter regions of RASSF1A was examined by methylation-specific polymerase chain reaction (MSP) in a cohort of 25 primary MBs, 9 primary SPNETs, 3 MB and 2 SPNET cell lines. RASSF1A-deficient PNET cell lines were treated with 5-aza-2'deoxycytidine, a demethylating agent, to explore the relationship between hypermethylation and the gene expression.


RESULTS
The results revealed no promoter hypermethylation of RASSF1A in 2 normal cerebellar and 5 normal cerebral tissue specimens examined. In contrast, promoter hypermethylation of RASSF1A was detected in 100% (25/25) of primary MBs, 6/9 of primary SPNETs, and all PNET cell lines. These results demonstrated that such epigenetic alteration was tumor-specific. The frequency of hypermethylation of RASSF1A in SPNETs was also found to be significantly lower than that in MBs (Fisher's exact test, P = 0.014). Treatment of RASSF1A-deficient PNET cell lines with 5-aza-2'deoxycytidine restored RASSF1A expression, providing evidence that promoter hypermethylation contributes to transcriptional silencing.


CONCLUSIONS
These results demonstrate that RASSF1A plays an important role in the development of intracranial PNETs. Different hypermethylation status of RASSF1A are found in PNET subtypes suggesting that MBs and SPNETs are epigenetical distinct tumors.
Chang
Qing
Q
Department of Pathology, Peking University Health Science Center, Beijing 100083, China. qingchang@bjmu.edu.cn
Ng
Ho-Keung
HK
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins