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DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis

Esteller, Manel; Fraga, Mario F.; Guo, Mingzhou; Garcia-Foncillas, Jesus; Hedenfalk, Ingrid LU ; Godwin, Andrew K.; Trojan, Joerg; Vaurs-Barriere, Catherine; Bignon, Yves-Jean and Ramus, Susan, et al. (2001) In Human Molecular Genetics 10(26). p.3001-3007
Abstract
Cancer cells have aberrant patterns of DNA methylation including hypermethylation of gene promoter CpG islands and global demethylation of the genome. Genes that cause familial cancer, as well as other genes, can be silenced by promoter hypermethylation in sporadic tumors, but the methylation of these genes in tumors from kindreds with inherited cancer syndromes has not been well characterized. Here, we examine CpG island methylation of 10 genes (hMLH1, BRCA1, APC, LKB1, CDH1, p16(INK4a), p14(ARF), MGMT, GSTP1 and RARbeta2) and 5-methylcytosine DNA content, in inherited (n = 342) and non-inherited (n = 215) breast and colorectal cancers. Our results show that singly retained alleles of germline mutated genes are never hypermethylated in... (More)
Cancer cells have aberrant patterns of DNA methylation including hypermethylation of gene promoter CpG islands and global demethylation of the genome. Genes that cause familial cancer, as well as other genes, can be silenced by promoter hypermethylation in sporadic tumors, but the methylation of these genes in tumors from kindreds with inherited cancer syndromes has not been well characterized. Here, we examine CpG island methylation of 10 genes (hMLH1, BRCA1, APC, LKB1, CDH1, p16(INK4a), p14(ARF), MGMT, GSTP1 and RARbeta2) and 5-methylcytosine DNA content, in inherited (n = 342) and non-inherited (n = 215) breast and colorectal cancers. Our results show that singly retained alleles of germline mutated genes are never hypermethylated in inherited tumors. However, this epigenetic change is a frequent second "hit", associated with the wild-type copy of these genes in inherited tumors where both alleles are retained. Global hypomethylation was similar between sporadic and hereditary cases, but distinct differences existed in patterns of methylation at non-familial genes. This study demonstrates that hereditary cancers "mimic" the DNA methylation patterns present in the sporadic tumors. (Less)
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Human Molecular Genetics
volume
10
issue
26
pages
3001 - 3007
publisher
Oxford University Press
external identifiers
  • pmid:11751682
  • wos:000172870300005
  • scopus:18244388241
ISSN
0964-6906
DOI
10.1093/hmg/10.26.3001
language
English
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yes
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0422aead-5239-4401-8a34-558274dc5569 (old id 1120263)
date added to LUP
2008-06-27 09:48:32
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2018-04-22 03:21:46
@article{0422aead-5239-4401-8a34-558274dc5569,
  abstract     = {Cancer cells have aberrant patterns of DNA methylation including hypermethylation of gene promoter CpG islands and global demethylation of the genome. Genes that cause familial cancer, as well as other genes, can be silenced by promoter hypermethylation in sporadic tumors, but the methylation of these genes in tumors from kindreds with inherited cancer syndromes has not been well characterized. Here, we examine CpG island methylation of 10 genes (hMLH1, BRCA1, APC, LKB1, CDH1, p16(INK4a), p14(ARF), MGMT, GSTP1 and RARbeta2) and 5-methylcytosine DNA content, in inherited (n = 342) and non-inherited (n = 215) breast and colorectal cancers. Our results show that singly retained alleles of germline mutated genes are never hypermethylated in inherited tumors. However, this epigenetic change is a frequent second "hit", associated with the wild-type copy of these genes in inherited tumors where both alleles are retained. Global hypomethylation was similar between sporadic and hereditary cases, but distinct differences existed in patterns of methylation at non-familial genes. This study demonstrates that hereditary cancers "mimic" the DNA methylation patterns present in the sporadic tumors.},
  author       = {Esteller, Manel and Fraga, Mario F. and Guo, Mingzhou and Garcia-Foncillas, Jesus and Hedenfalk, Ingrid and Godwin, Andrew K. and Trojan, Joerg and Vaurs-Barriere, Catherine and Bignon, Yves-Jean and Ramus, Susan and Benitez, Javier and Caldes, Trinidad and Akiyama, Yoshimitsu and Yuasa, Yusuhito and Launonen, Virpi and Canal, Maria Jesus and Rodriguez, Roberto and Capella, Gabriel and Peinado, Miguel Angel and Borg, Åke and Aaltonen, Lauri A. and Ponder, Bruce A. and Baylin, Stephen B. and Herman, James G.},
  issn         = {0964-6906},
  language     = {eng},
  number       = {26},
  pages        = {3001--3007},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis},
  url          = {http://dx.doi.org/10.1093/hmg/10.26.3001},
  volume       = {10},
  year         = {2001},
}