High promoter hypermethylation frequency of p14/ARF in supratentorial PNET but not in medulloblastoma.
OBJECTIVE
Medulloblastoma (MB) is the most common primitive neuroectodermal tumour (PNET) of the central nervous system. Although supratentorial PNET (sPNET) and MB are histologically similar, their clinical behaviour differs, sPNET being more aggressive than MB. The aim of this study was to determine whether sPNET and MB are genetically different entities.


RESULTS
We investigated 32 PNET primary tumour samples (23 MB and nine sPNET) and four PNET cell lines, for the presence of CDKN2A homozygous deletions at exon 1-alpha of p16/INK4 and exon 1-beta of p14/ARF, and promoter hypermethylation of both genes. No homozygous deletion of either p16/INK4 or p14/ARF was demonstrated in any of the PNET primary tumour samples. Methylation of p16/INK4 was found in one of six sPNET and in one of 23 MB, while p14/ARF methylation was observed in three of six sPNET and in three of 21 MB. No methylation of p16/INK4 or p14/ARF was found in any of the PNET cell lines analysed. The three MB cell lines did not show p16/INK4 expression, and only the MB Daoy cell line (homozygously deleted at CDKN2A) presented loss of p14/ARF expression.


CONCLUSIONS
Our results in this limited series of central PNET show that p14/ARF is frequently involved in PNET carcinogenesis, with a higher frequency, but not statistically significant, for sPNET than for MB.
Inda
M M
MM
Laboratorio de Neuro-Oncología Molecular, Universidad de Navarra, Pamplona, Spain.
Muñoz
J
J
Coullin
P
P
Fauvet
D
D
Danglot
G
G
Tuñón
T
T
Bernheim
A
A
Castresana
J S
JS
D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015173:Supratentorial Neoplasms / Q000235:genetics / Q000473:pathology*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF