The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma

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 a...

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Bibliographic Details
Published in:British journal of cancer 2012-10, Vol.107 (8), p.1423-1432
Main Authors: HATZIMICHAEL, E, LO NIGRO, C, PAPOUDOU-BAI, A, BAI, M, SCHMID, P, STEBBING, J, BOWER, M, DYER, Mjs, KARRAN, L. E, ELGUETAKARSTEGL, C, FARRELL, P. J, THOMPSON, A, LATTANZIO, L, BRIASOULIS, E, CROOK, T, SYED, N, SHAH, R, DASOULA, A, JANCZAR, K, VIVENZA, D, MONTEVERDE, M, MERLANO, M
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bone marrow
Breast cancer
Cancer research
Cartilage
Cell Line, Tumor
Collagen
Collagen - genetics
Collagen - metabolism
CpG Islands - genetics
Cyclin-dependent kinases
Epigenetics
Gene Expression Regulation
Gene Silencing
Genes
Genetics and Genomics
Hematologic and hematopoietic diseases
Hospitals
Humans
Kinases
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma
Lymphoma, B-Cell - genetics
Lymphoma, B-Cell - metabolism
Medical research
Medical sciences
Methylation
Oncology
Procollagen-Proline Dioxygenase - genetics
Procollagen-Proline Dioxygenase - metabolism
Proteins
Tumors
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Summary: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. 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. 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. Methylation of C-P3H and C-P4H is common in B lymphomas and may have utility in differentiating disease subtypes.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2012.380