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 medullobla stomas (MBs), and the major breakpoint interval has been localized to chrom osome segment 17011.2. Based on several reports linking aberrant DNA methyl ation and chromosomal disruption, we examined the methylation pattern in th is region by employing restriction landmark genomic scanning (RLGS), Severa l CpG islands located in the major breakpoint cluster region were identifie d using a bacterial artificial chromosome (BAC) contig of the breakpoint re gion. A long-range methylation map was established for 20 MBs and 5 suprate ntorial primitive neuroectodermal tumors (stPNETs). Selected CpG islands we re examined using Southern and bisulfite sequencing analysis. Aberrantly hy permethylated CpG islands in 17p11.2 were found in 33% of MBs. Interestingl y, one CpG island was methylated in MBs, but not in any of the examined stP NETs. A BAC clone covering three of the methylated CpG islands was partiall y sequenced in the search for a potential tumor suppressor gene. None of th e expressed sequence tag sequences and full-length mouse/human cDNAs that w ere associated with aberrant methylation showed a change in expression leve ls due to methylation. The potential link between chromosomal instability i n 17p11.2 and hypermethylation in this region is discussed. (C) 2001 Wiley- Liss, Inc.