Koos Boeve

158 Chapter 8 proliferation [38]. Signal-induced proliferation associated protein 1 ( SIPA1 ) is located at the 11q13 chromosome close to CCND1 (cyclin D1) and is known for influencing growth factors and cytokines by regulating RAP1 in hematopoietic cells [39,40]. Loss of SIPA1 resulted in myeloproliferative disorders in mice [40]. The interaction between SIPA1 and RAP1 is also associated with metastasis in breast and prostate cancer by mediating cell adhesion signaling and metastasis suppressor gene signaling [40]. Recently, SIPA1 was found to be overexpressed in OSCC and correlated to lymph node metastasis [41]. C11orf85 also called MAJIN (membrane anchored junction protein) plays a role in telomere attachment to the inner nuclear membrane during meiosis [42,43]. C11orf85 / MAJIN is related to cancer as one of the genes in a 92-gene signature that is prognostic for overall survival inmultiplemyeloma patients [44]. Currently, no studies are available that report the exact role of C11orf85 / MAJIN in oncogenesis. The biological significance of these three methylated genes in OSCC has not been elucidated in great detail and needs further investigation in future. CONCLUSIONS In conclusion, using the methylome of 12 OSCC tissue samples based on a genome-wide methylation screening approach, we have identified several novel biomarkers commonly methylated in OSCC. With one of these methylation markers ( KCNA5 ) cells in saliva that are associatedwithOSCC patients could be detectedwith a high diagnostic potential. Moreover, it is of interest to perform a larger scale evaluation for KCNA5 combined with TIMP3, given the 100% diagnostic potential found for detecting OSCC cells in saliva. Irrespective of the small study size, our findings demonstrate the high sensitivity of Quantitative Methylation Specific PCR for detecting methylation on saliva cell DNA. DNA methylation detection using saliva has potential as an easy, low-cost, non-invasive and accurate diagnostic tool to improve the early detection of local recurrences or second primary tumors in OSCC. Our findings warrant evaluation of the clinical relevance of these methylation markers in larger cohorts.