The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma

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. ThompsonE. Briasoulis, T. Crook

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    9 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)1423-1432
    Number of pages10
    JournalBritish Journal of Cancer
    Volume107
    Issue number8
    DOIs
    Publication statusPublished - 2012

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    Hatzimichael, E., Lo Nigro, C., Lattanzio, L., Syed, N., Shah, R., Dasoula, A., Janczar, K., Vivenza, D., Monteverde, M., Merlano, M., Papoudou-Bai, A., Bai, M., Schmid, P., Stebbing, J., Bower, M., Dyer, M. J. S., Karran, L. E., Elguetakarstegl, C., Farrell, P. J., ... Crook, T. (2012). The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma. British Journal of Cancer, 107(8), 1423-1432. https://doi.org/10.1038/bjc.2012.380