Understanding oral cancer in the genome era

Abstract

Completion of the human genome project approximately 15 years ago was followed closely by advancements in array technology. Investigators quickly applied this new powerful tool to the genomic and proteomic study of oral squamous cell carcinoma (OSCC). Resultant publications documented chromosome, gene, mRNA, and protein alterations that characterize oral cancer. In this review, we summarize how the genomic, proteomic, and epigenetic array studies have provided insight into the process of oral carcinogenesis. We discuss the significant limitations and requirement for validation of these array studies. We also review the manner in which state-of-the-art, high-throughput approaches are being used to search for salivary and serum oral cancer biomarkers.

Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance

“…Despite the advances in diagnosis and therapeutic approaches, the mortality and morbidity rates have not improved over the past decades [5]. Copy number alterations promote genetic instability in cancer and lack of improvement in the clinical outcomes most probably reflects the paucity in the knowledge that explains how genetic instabilities in oral cancer contribute in oral carcinogenesis [6, 7]. Moreover, molecular heterogeneity is another issue that should be kept in mind [8].…”

Model of Chromosomal Instability in Oral Carcinogenesis and Progression

“…Clearly, what is still strongly needed in the model system of oral preneoplasia and neoplasia is a better understanding of the origin and dynamic evolution of chromosomal instability, chromosomal aberrations and aneuploidy (Albertson et al, 2003;Asteriti et al, 2010;Compton et al, 2011;Geigl et al, 2008;Giet et al, 2005;Kops et al, 2005;Lingen et al, 2011;Sieber et al, 2003;Suijkerbuijk & Kops, 2008;Thompson et al, 2010;Viet & Schmidt, 2010). In other models of cancer genesis and progression, like the colorectal adenoma-carcinoma sequence, the Barrett's esophagus and the ulcerative colitis transition to carcinoma, the role of APC and TP53 has been highlighted (Fodde et al, 2001;Giaretti et al, 2004;Rabinovitch et al, 2004).…”

Oral Cavity and Oropharyngeal Squamous Cell Carcinoma Genomics

“…More recently, microarray-based assays, or array CGH, have been developed to overcome the pitfalls of karyotype and standard CGH-based analyses. Array CGH, which utilizes bacterial artificial chromosome (BAC) arrays, allows for the high-throughput analysis of DNA copy number variations throughout the whole genome and allows high-resolution mapping of these changes directly onto genomic sequence 2,59 . The resolution of array CGH platforms continues to improve to sub-megabase levels, so that variations ranging from gene-size aberrations to entire chromosomal arms may now be detected 65 .…”

“…However, most studies to date in HNSCC have analyzed the methylation status of individual genes previously implicated in carcinogenesis. Several techniques have been used to evaluate genome-wide methylation, including restriction landmark genomic scanning (RLGS), methylation-specific restriction enzyme (MSRE) analysis, and arbitrarily-primed PCR 59,78 .…”