Tumor suppressor gene methylation in follicular lymphoma: a comprehensive review.
Transcriptional silencing of tumor suppressor genes, associated with DNA methylation, is a common epigenetic event in hematologic malignancies. Although DNA hypermethylation of CpG islands is well described in acute leukemias and myelodysplastic syndromes, much less is known of the specific methylation changes that commonly occur in follicular B cell lymphomas. Earlier methylation studies of follicular lymphoma involved only cell lines; however there is a growing literature of methylation changes in primary human FL samples. Published studies of primary follicular lymphoma specimens have demonstrated that: androgen receptor, SHP1, and death-associated protein kinase genes are commonly methylated. By contrast, the cyclin dependent kinase inhibitors p15, p16, and p57 are uncommon epigenetic events in follicular lymphoma. Methylation of cyclin dependent kinase inhibitors is more common in high grade lymphomas, and may be an important step in the progression and transformation of follicular lymphoma. Further methylation studies in follicular lymphoma should investigate the prognostic and therapeutic significance of these epigenetic changes and investigate methylation of other genes. Finally, reactivation of methylated tumor suppressor genes through the use of hypomethylating agents is a promising and novel approach to the treatment of indolent and transformed follicular lymphomas.
Hayslip
John
J
Hollings Cancer Center, Medical University of South Carolina, Clinical Sciences Building Room 903, PO Box 250635, Charleston, SC 29425, USA. hayslip@musc.edu
Montero
Alberto
A
D000818:Animals; D017305:Annexin A1 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D064550:Death-Associated Protein Kinases; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D053712:Interleukin-12 Receptor beta 2 Subunit / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000097642:GADD45 Proteins
D017305:Annexin A1; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases; D064550:Death-Associated Protein Kinases; D051549:Glutathione S-Transferase pi; D053712:Interleukin-12 Receptor beta 2 Subunit; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D011944:Receptors, Androgen; D025521:Tumor Suppressor Proteins; D000097642:GADD45 Proteins; C496126:PLK2 protein, human