Abstract:
:Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this mechanism to contribute to tumor development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ES cells, suggesting that their aberrant methylation may reflect developmental processes. We investigated this possibility by analyzing promoter methylation in 19 breast cancer cell lines and 47 primary breast tumors. In cell lines, we defined 120 genes that were significantly repressed in association with methylation (SRAM). These genes allowed the unsupervised segregation of cell lines into epithelial (EPCAM+ve) and mesenchymal (EPCAM-ve) lineages. However, the methylated genes were already repressed in normal cells of the same lineage, and >90% could not be derepressed by treatment with 5-aza-2'-deoxycytidine. The tumor suppressor genes APC and CDH1 were among those methylated in a lineage-specific fashion. As predicted by the epithelial nature of most breast tumors, SRAM genes that were methylated in epithelial cell lines were frequently aberrantly methylated in primary tumors, as were genes specifically repressed in normal epithelial cells. An SRAM gene expression signature also correctly identified the rare claudin-low and metaplastic tumors as having mesenchymal characteristics. Our findings implicate aberrant DNA methylation as a marker of cell lineage rather than tumor progression and suggest that, in most cases, it does not cause the repression with which it is associated.
journal_name
Proc Natl Acad Sci U S Aauthors
Sproul D,Nestor C,Culley J,Dickson JH,Dixon JM,Harrison DJ,Meehan RR,Sims AH,Ramsahoye BHdoi
10.1073/pnas.1013224108subject
Has Abstractpub_date
2011-03-15 00:00:00pages
4364-9issue
11eissn
0027-8424issn
1091-6490pii
1013224108journal_volume
108pub_type
杂志文章abstract::The previously described peptide material that reacts with antibodies to gastrin and is found in the central nervous system of various vertebrates is present in only the 100,000 X g pellet of postmortem human cerebral cortical grey matter. This immunoreactive material, extractable in boiling water, is biologically act...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.1.524
更新日期:1978-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.7.4209
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.97.1.518
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0611691104
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更新日期:2017-09-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0607055103
更新日期:2006-12-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1100292108
更新日期:2011-06-28 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.93.14.7091
更新日期:1996-07-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1616340114
更新日期:2017-01-31 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.14.5269
更新日期:1988-07-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.96.16.9374
更新日期:1999-08-03 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.9.4042
更新日期:1993-05-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.97.15.8340
更新日期:2000-07-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.8.3571
更新日期:1995-04-11 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0913815107
更新日期:2010-06-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.24.9233
更新日期:1987-12-01 00:00:00
abstract::A theoretical description of aqueous hydration in the minor groove of a B-form DNA is presented on the basis of a liquid-state Monte Carlo computer simulation on a system consisting of the oligonucleotide duplex d(CGCGAATTCGCG).d(GCGCTTAAGCGC) in a canonical B-form together with 1777 water molecules contained in a hex...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.6.1836
更新日期:1988-03-01 00:00:00
abstract::We have examined the extent of tyrosine phosphorylation of talin, a component of the cytoskeleton localized in the focal adhesions and, therefore, a potential substrate of p60v-src, the transforming protein of Rous sarcoma virus. p60v-src is a tyrosine kinase that induces high levels of phosphotyrosine and the disorga...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.15.5507
更新日期:1986-08-01 00:00:00
abstract::Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1406103111
更新日期:2014-06-10 00:00:00
abstract::Erythropoietin, the major hormone controlling red-cell production, is regulated in part through oxygen-dependent changes in the rate of transcription of its gene. Using transient transfection in HepG2 cells, we have defined a DNA sequence, located 120 base pairs 3' to the poly(A)-addition site of the mouse erythropoie...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.23.10553
更新日期:1991-12-01 00:00:00
abstract::The AML1 gene, located on chromosome 21, is involved in several distinct chromosomal translocations in human leukemia. In t(8;21) acute myelogenous leukemia (AML), the AML1 gene is juxtaposed to the ETO gene located on chromosome 8, generating an AML1/ETO fusion protein. Both AML1/ETO and the AML1 proteins recognize t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.24.14059
更新日期:1996-11-26 00:00:00
abstract::Short oxygen-halogen interactions have been known in organic chemistry since the 1950s and recently have been exploited in the design of supramolecular assemblies. The present survey of protein and nucleic acid structures reveals similar halogen bonds as potentially stabilizing inter- and intramolecular interactions t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407607101
更新日期:2004-11-30 00:00:00