Aberrant hypermethylation of the major breakpoint cluster region in 17p11.2 in medulloblastomas but not supratentorial PNETs.
Deletions of 17p have been consistently reported in up to 50% of medulloblastomas (MBs), and the major breakpoint interval has been localized to chromosome segment 17p11.2. Based on several reports linking aberrant DNA methylation and chromosomal disruption, we examined the methylation pattern in this region by employing restriction landmark genomic scanning (RLGS). Several CpG islands located in the major breakpoint cluster region were identified using a bacterial artificial chromosome (BAC) contig of the breakpoint region. A long-range methylation map was established for 20 MBs and 5 supratentorial primitive neuroectodermal tumors (stPNETs). Selected CpG islands were examined using Southern and bisulfite sequencing analysis. Aberrantly hypermethylated CpG islands in 17p11. 2 were found in 33% of MBs. Interestingly, one CpG island was methylated in MBs, but not in any of the examined stPNETs. A BAC clone covering three of the methylated CpG islands was partially sequenced in the search for a potential tumor suppressor gene. None of the expressed sequence tag sequences and full-length mouse/human cDNAs that were associated with aberrant methylation showed a change in expression levels due to methylation. The potential link between chromosomal instability in 17p11.2 and hypermethylation in this region is discussed.
Frühwald
M C
MC
Division of Human Cancer Genetics, Department of Molecular Virology Immunology and Medical Genetics, The Ohio State University and the Comprehensive Cancer Center, Columbus, Ohio, USA. fruhworld@uni-muenster.de
O'Dorisio
M S
MS
Dai
Z
Z
Rush
L J
LJ
Krahe
R
R
Smiraglia
D J
DJ
Pietsch
T
T
Elsea
S H
SH
Plass
C
C
D000293:Adolescent; D000328:Adult; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage / Q000235:genetics*; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics*; D015173:Supratentorial Neoplasms / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D014178:Translocation, Genetic