title: The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma.
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 α subunit, encoded by the P4HA1, P4HA2 and P4HA3 genes and a constant β 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 Burkitt's lymphoma.
  
  
  CONCLUSIONS
  Methylation of C-P3H and C-P4H is common in B lymphomas and may have utility in differentiating disease subtypes.
authors.affiliation: Department of Hematology, University Hospital of Ioannina, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Hatzimichael
authors.forename: C
authors.initials: C
authors.lastname: Lo Nigro
authors.forename: L
authors.initials: L
authors.lastname: Lattanzio
authors.forename: N
authors.initials: N
authors.lastname: Syed
authors.forename: R
authors.initials: R
authors.lastname: Shah
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authors.initials: A
authors.lastname: Dasoula
authors.forename: K
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authors.lastname: Janczar
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authors.initials: D
authors.lastname: Vivenza
authors.forename: M
authors.initials: M
authors.lastname: Monteverde
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authors.lastname: Merlano
authors.forename: A
authors.initials: A
authors.lastname: Papoudou-Bai
authors.forename: M
authors.initials: M
authors.lastname: Bai
authors.forename: P
authors.initials: P
authors.lastname: Schmid
authors.forename: J
authors.initials: J
authors.lastname: Stebbing
authors.forename: M
authors.initials: M
authors.lastname: Bower
authors.forename: M J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: L E
authors.initials: LE
authors.lastname: Karran
authors.forename: C
authors.initials: C
authors.lastname: ElguetaKarstegl
authors.forename: P J
authors.initials: PJ
authors.lastname: Farrell
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: E
authors.initials: E
authors.lastname: Briasoulis
authors.forename: T
authors.initials: T
authors.lastname: Crook
mesh_terms: D045744:Cell Line, Tumor; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism; D008745:Methylation; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D003094:Collagen; D011393:Procollagen-Proline Dioxygenase