SPARC and DNA methylation: Possible diagnostic and therapeutic implications in gastrointestinal cancers |
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| Authors: | Ganji Purnachandra Nagaraju Bassel F. EI-Rayes |
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| Affiliation: | Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States |
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| Abstract: | DNA methylation is a major contributor to epigenetic alterations and as such is a potential biomarker and therapeutic target in gastrointestinal malignancies. DNA methylation is commonly observed in several Gastrointestinal (GI) malignancies including pancreatic and colorectal cancer. Methylation results in decreased expression of tumor suppressor genes. Secreted protein acidic and rich in cysteine (SPARC) is a tumor suppressor gene that can be functionally inactivated through methylation. SPARC is commonly dysregulated in GI malignancies. Inhibition of DNA methylation can reverse the silencing of SPARC. In the present review, we will discuss recent advances in our understanding of the features of DNA methylation that pertain to SPARC, focusing on their functional and clinical relevance in GI carcinogenesis. |
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| Keywords: | GI, gastrointestinal SPARC, secreted protein acidic and rich in cysteine TSLC1, tumor suppressor in lung cancer 1 CRCs, colorectal cancers DNMTs, DNA methyltransferases SAM, S-adenosyl methionine TRDMT1, tRNA aspartic acid methyltransferase1 PCR, polymerase chain reaction RT-QMSP, real-time quantitative methylation-specific PCR GWS, genome-wide screening DMH, differential methylation hybridization MMASS, microarray-based methylation assessment of single sample MBD, methyl cytosine DNA binding domain CIMP, CpG island methylated IPMN, intraductal papillary mucinous neoplasms MSI, microsatellite instable CIN, chromosomal instable phenotype COBRA, combined bisulfite restriction analysis MSP, methylation-specific PCR BSP, bisulfite-specific PCR HCC, hepatocellular carcinoma MMPs, matrix metalloproteinases PDGF, platelet-derived growth factor VEGF, vascular endothelial growth factor |
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