Distinct methylation changes at the IGF2-H19 locus in congenital growth disorders and cancer

Adele Murrell, Yoko Ito, Gaetano Verde, Joanna Huddleston, Kathryn Woodfine, Margherita Cirillo Silengo, Filippo Spreafico, Daniela Perotti, Agostina De Crescenzo, Angela Sparago, Flavia Cerrato, Andrea Riccio

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87 Citations (Scopus)

Abstract

Differentially methylated regions (DMRs) are associated with many imprinted genes. In mice methylation at a DMR upstream of the H19 gene known as the Imprint Control region (IC1) is acquired in the male germline and influences the methylation status of DMRs 100 kb away in the adjacent Insulin-like growth factor 2 (Igf2) gene through long-range interactions. In humans, germline-derived or post-zygotically acquired imprinting defects at IC1 are associated with aberrant activation or repression of IGF2, resulting in the congenital growth disorders Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, respectively. In Wilms tumour and colorectal cancer, biallelic expression of IGF2 has been observed in association with loss of methylation at a DMR in IGF2. This DMR, known as DMR0, has been shown to be methylated on the silent maternal IGF2 allele presumably with a role in repression. The effect of IGF2 DMR0 methylation changes in the aetiology of BWS or SRS is unknown.
Original languageEnglish
Article numbere1849
JournalPLoS ONE
Volume3
Issue number3
DOIs
Publication statusPublished - 2008

Keywords

  • DNA Methylation
  • Growth Disorders
  • Humans
  • Insulin-Like Growth Factor II
  • Neoplasms
  • RNA, Long Noncoding
  • RNA, Untranslated

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