High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer.

Published online

Journal Article

Cell surface mannose 6-phosphate/insulin-like growth factor II receptors (M6P/IGF2R) bind and target exogenous insulin-like growth factor II (IGF2) to the prelysosomes where it is degraded. Loss of heterozygosity (LOH) for M6P/IGF2R is found in cancers, with mutational inactivation of the remaining allele. We exploited the normal allele-specific differential methylation of the M6P/IGF2R intron 2 CpG island to rapidly evaluate potential LOH in ovarian cancers, since every normal individual is informative. To this end, we developed a method for bisulfite modification of genomic DNA in 96-well format that allows for rapid methylation profiling. We identified ovarian cancers with M6P/IGF2R LOH, but unexpectedly also found frequent abnormal acquisition of methylation on the paternally inherited allele at intron 2. These results demonstrate the utility of our high-throughput method of bisulfite modification for analysis of large sample numbers. They further show that the methylation status of the intron 2 CpG island may be a useful indicator of LOH and biomarker of disease.

Full Text

Duke Authors

Cited Authors

  • Huang, Z; Wen, Y; Shandilya, R; Marks, JR; Berchuck, A; Murphy, SK

Published Date

  • 2006

Published In

Volume / Issue

  • 34 / 2

Start / End Page

  • 555 - 563

PubMed ID

  • 16432260

Pubmed Central ID

  • 16432260

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkj468

Language

  • eng

Conference Location

  • England