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

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

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...

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Main Authors: Huang, Zhiqing, Wen, Yaqing, Shandilya, Ruby, Marks, Jeffrey R., Berchuck, Andrew, Murphy, Susan K.
Format: Online
Language:English
Published: Oxford University Press 2006
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1345698/
id pubmed-1345698
recordtype oai_dc
spelling pubmed-13456982006-01-25 High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer Huang, Zhiqing Wen, Yaqing Shandilya, Ruby Marks, Jeffrey R. Berchuck, Andrew Murphy, Susan K. 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. Oxford University Press 2006 2006-01-23 /pmc/articles/PMC1345698/ /pubmed/16432260 http://dx.doi.org/10.1093/nar/gkj468 Text en © The Author 2006. Published by Oxford University Press. All rights reserved
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Huang, Zhiqing
Wen, Yaqing
Shandilya, Ruby
Marks, Jeffrey R.
Berchuck, Andrew
Murphy, Susan K.
spellingShingle Huang, Zhiqing
Wen, Yaqing
Shandilya, Ruby
Marks, Jeffrey R.
Berchuck, Andrew
Murphy, Susan K.
High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer
author_facet Huang, Zhiqing
Wen, Yaqing
Shandilya, Ruby
Marks, Jeffrey R.
Berchuck, Andrew
Murphy, Susan K.
author_sort Huang, Zhiqing
title High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer
title_short High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer
title_full High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer
title_fullStr High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer
title_full_unstemmed High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer
title_sort high throughput detection of m6p/igf2r intronic hypermethylation and loh in ovarian cancer
description 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.
publisher Oxford University Press
publishDate 2006
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1345698/
_version_ 1611380316684943360

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