TY - JOUR
T1 - The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma
AU - Hatzimichael, E.
AU - Lo Nigro, C.
AU - Lattanzio, L.
AU - Syed, N.
AU - Shah, R.
AU - Dasoula, A.
AU - Janczar, K.
AU - Vivenza, D.
AU - Monteverde, M.
AU - Merlano, M.
AU - Papoudou-Bai, A.
AU - Bai, M.
AU - Schmid, P.
AU - Stebbing, J.
AU - Bower, M.
AU - Dyer, M.J.S.
AU - Karran, L.E.
AU - Elguetakarstegl, C.
AU - Farrell, P.J.
AU - Thompson, A.
AU - Briasoulis, E.
AU - Crook, T.
N1 - Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84867405334
U2 - 10.1038/bjc.2012.380
DO - 10.1038/bjc.2012.380
M3 - Article
C2 - 22955849
AN - SCOPUS:84867405334
SN - 0007-0920
VL - 107
SP - 1423
EP - 1432
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -