Six anaplastic iEPN-PFs were subjected to transcriptomic analysis and FISH for p16 loss and gains of 1q, and compared with anaplastic PF EPNs from older children.
The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs.
Methylation of p16 (INK4A), p14 (ARF), TIMP3, CDH1, p15 (INK4B )and DAPK1 in medulloblastoma (MB) and ependymoma has been discussed controversially in the literature.
The present objective was, for a sample of 27 children with intracranial EP and 7 with CPP, to describe and compare the methylation status of 19 genes (with current HUGO symbol, if any): p15INK4a (CDKN2B), p16INK4a and p14ARF (both CDKN2A), APC, RB1, RASSF1A (RASSF1), BLU (ZMYND10) FHIT, RARB, MGMT, DAPK (DAPK1), ECAD (CDH1), CASP8, TNFRSF10C, TNFRSF10D, FLIP (CFLAR), INI1 (SMARCB1), TIMP3, and NF2.
To investigate the role of aberrant epigenetic events in ependymoma and identify critical genes in its pathogenesis, the methylation status of nine tumour suppressor genes (TSGs: p14(ARF), p15(INK4B), p16(INK4A), CASP8, MGMT, TIMP3, TP73, RB1 and RASSF1A) was assessed.
The frequencies of hypermethylation for the 10 genes were as follows, in oligodendrogliomas and ependymomas, respectively: 80% and 28% for MGMT; 70% and 28% for GSTP1; 66% and 57% for DAPK; 44% and 28% for TP14(ARF); 39% and 0% for THBS1; 24% and 28% for TIMP3; 24% and 14% for TP73; 22% and 0% for TP16(INK4A); 3% and 14% for RB1; and 0% in both neoplasms for TP53.
Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas.