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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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Autores principales: Huang, Zhiqing, Wen, Yaqing, Shandilya, Ruby, Marks, Jeffrey R., Berchuck, Andrew, Murphy, Susan K.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1345698/
https://www.ncbi.nlm.nih.gov/pubmed/16432260
http://dx.doi.org/10.1093/nar/gkj468
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author Huang, Zhiqing
Wen, Yaqing
Shandilya, Ruby
Marks, Jeffrey R.
Berchuck, Andrew
Murphy, Susan K.
author_facet Huang, Zhiqing
Wen, Yaqing
Shandilya, Ruby
Marks, Jeffrey R.
Berchuck, Andrew
Murphy, Susan K.
author_sort Huang, Zhiqing
collection PubMed
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.
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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. Nucleic Acids Res 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
spellingShingle Article
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
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1345698/
https://www.ncbi.nlm.nih.gov/pubmed/16432260
http://dx.doi.org/10.1093/nar/gkj468
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