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DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis

Author:
  • Manel Esteller
  • Mario F. Fraga
  • Mingzhou Guo
  • Jesus Garcia-Foncillas
  • Ingrid Hedenfalk
  • Andrew K. Godwin
  • Joerg Trojan
  • Catherine Vaurs-Barriere
  • Yves-Jean Bignon
  • Susan Ramus
  • Javier Benitez
  • Trinidad Caldes
  • Yoshimitsu Akiyama
  • Yusuhito Yuasa
  • Virpi Launonen
  • Maria Jesus Canal
  • Roberto Rodriguez
  • Gabriel Capella
  • Miguel Angel Peinado
  • Åke Borg
  • Lauri A. Aaltonen
  • Bruce A. Ponder
  • Stephen B. Baylin
  • James G. Herman
Publishing year: 2001
Language: English
Pages: 3001-3007
Publication/Series: Human Molecular Genetics
Volume: 10
Issue: 26
Document type: Journal article
Publisher: Oxford University Press

Abstract english

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.

Keywords

  • Medical Genetics

Other

Published
  • ISSN: 0964-6906
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90