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

Abstract:

: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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

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

doi

10.1093/nar/gkj468

keywords:

subject

Has Abstract

pub_date

2006-01-23 00:00:00

pages

555-63

issue

2

eissn

0305-1048

issn

1362-4962

pii

34/2/555

journal_volume

34

pub_type

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