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The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma

The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma

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Authors

  • E. Hatzimichael
  • C. Lo Nigro
  • L. Lattanzio
  • N. Syed
  • R. Shah
  • A. Dasoula
  • K. Janczar
  • D. Vivenza
  • M. Monteverde
  • M. Merlano
  • A. Papoudou-Bai
  • M. Bai
  • P. Schmid
  • J. Stebbing
  • M. Bower
  • M.J.S. Dyer
  • L.E. Karran
  • C. Elguetakarstegl
  • P.J. Farrell
  • A. Thompson
  • And 2 others
  • E. Briasoulis
  • T. Crook

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Info

Original languageEnglish
Pages1423-1432
Number of pages10
JournalBritish Journal of Cancer
Journal publication date2012
Volume107
Issue8
DOIs
StatePublished

Abstract

Background: Prolyl hydroxylation is a post-translational modification that affects the structure, stability and function of proteins including collagen by catalysing hydroxylation of proline to hydroxyproline through action of collagen prolyl hydroxylases3 (C-P3H) and 4 (C-P4H). Three C-P3Hs (nomenclature was amended according to approval by the HGNC symbols and names at http://www.genenames.org/ and Entrez database at http://www.ncbi.nlm.nih.gov/ gene) leucineproline-enriched proteoglycan (leprecan) 1 (Lepre1), leprecan-like 1 (Leprel1), leprecan-like 2 (Leprel2) and two paralogs Cartilage-Related Protein (CRTAP) and leprecan-like 4 (Leprel4) are found in humans. The C-P4Hs are tetrameric proteins comprising a variable a subunit, encoded by the P4HA1, P4HA2 and P4HA3 genes and a constant ß subunit encoded by P4HB. Methods: We used RT-PCR, qPCR, pyrosequencing, methylation-specific PCR, western blotting and immunohistochemistry to investigate expression and regulation of the C-P3H and C-P4H genes in B lymphomas and normal bone marrow. Results: C-P3H and C-P4H are downregulated in lymphoma. Down-regulation is associated with methylation in the CpG islands and is detected in almost all common types of B-cell lymphoma, but the CpG islands are unmethylated or methylated at lower levels in DNA isolated from normal bone marrow and lymphoblastoid cell lines. Methylation of multiple C-P3H and C-P4H genes is present in some lymphomas, particularly Burkitts lymphoma. Conclusions: Methylation of C-P3H and C-P4H is common in B lymphomas and may have utility in differentiating disease subtypes. © 2012 Cancer Research UK.

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