Elucidation of the Molecular Mechanisms for Aberrant Expression of Breast Cancer Specific Gene 1 in Invasive and Metastatic Breast Carcinomas

摘要

We demonstrate that synuclein-gamma (SNCG) also named BCSG1 is abnormally expressed in a high percentage (67.5%) of tumor tissues of diversified cancer types including liver, esophagus, colon, gastric, lung, prostate, cervical, and breast cancer but rarely expressed in tumor matched non neoplastic adjacent tissues (NNAT) (0.6%). Expressions of SNCG protein in different cancer types all display stage-specific patterns of very low expression in stage I and high expression in stages II-IV. Importantly, we observe a strong association between SNCG protein expression in primary tumors with distant metastasis in patients regardless of the cancer type (60.6%, p< 0.001). By performing genomic sequencing and methylation-specific PCR assays, we identify an inclusive demethylation of CpG sites within the CpG island of SNCG gene in every tumor sample (100%) across all cancer types, illustrating a universal loss of the epigenetic control of SNCG gene expression in tumors and further demonstrating that the demethylation of SNCG CpG island is primarily responsible for the aberrant expression of SNCG protein in cancerous tissues. These new findings strongly suggest that reactivation of SNCG gene expression by DNA demethylation is a common critical contributing factor to. malignant progression of many solid tumors and its express in primary carcinomas is an effective molecular indicator of distant metastasis.