Differential loss of expression of common fragile site genes between oral tongue and oropharyngeal squamous cell carcinomas

Abstract

The common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. A number of the CFSs have been found to span genes that extend over large genomic regions (>700 kb). The expression of these genes is frequently abrogated in a number of different cancers and several of them have already been shown to function as tumor suppressor genes, both in vitro and in vivo. We analyzed the expression of 14 large CFS genes in two distinct groups of head and neck cancers using real-time RT-PCR. The first were oral tongue squamous cell carcinomas (SCCs) and the second were base of tongue/tonsillar (oropharyngeal) SCCs. These two groups were previously examined for the presence of human papillomavirus (HPV) and while 46% of the oropharyngeal cancers were positive for HPV16 only one of 52 oral cancers contained HPV16 sequences. We observed a distinct pattern of loss of expression of the large CFS genes in the two groups of head and neck cancers. In addition, there was no correlation between the relative instability in different CFS regions and which genes were inactivated. Thus, this report demonstrates another distinction between these two groups of head and neck cancer. In addition, it suggests that there is selection for loss of expression of specific CFS genes in these cancers.

Oral tongue squamous cell carcinoma: recurrent disease is associated with histopathologic risk score and young age

“…It is assumed that patients with HPV-associated head and neck SCC have a better prognosis, because of the lack of the Weld cancerization as in the classic form of SCC (Fakhry et al 2008;Liang et al 2008). However, in HPV-associated head and neck SCC the most common regions are the base of the tongue, the tonsillar region and the oropharynx (Soderberg et al 2008) and not the oral tongue-the focus of the current study. Furthermore, the incidence of HPV in oral tongue cancer in the "young" population (<45 year) was found to be low and is unlikely to constitute a signiWcant factor in the rising trends of oral tongue cancer in this population (Liang et al 2008).…”

Circular RNAs and their roles in head and neck cancers

“…This is because HNCs are relatively heterogeneous diseases that occur in complex anatomical structures, and different etiological factors and pathological and biological molecular changes are responsible for different subtypes of HNCs [148,149]. For example, the loss of expression of common fragile site genes [150] and Poor overall survival, poor radiosensitivity and serve as independent prognostic factors (HR = 3.03, p = 0.02) [147] Note: HNSCC head and neck squamous cell carcinoma, OSCC oral squamous cell carcinoma, LSCC laryngeal squamous cell carcinoma, NPC nasopharyngeal carcinoma, "-" means unannotated or not investigated in the paper, "*" means based on speculation but not validated clinically methylation of tumor-related genes [151] presented site-specificity in different subtypes of HNCs. Given the differentially expressed miRNAs in HNCs located at various places [152] and the tissue-specificity of cir-cRNAs, the circRNAs in HNCs may be differentially dysregulated according to the site of the primary tumor (Table 4).…”

Base of tongue cancer—is it tongue cancer located at the base of the tongue, or is it a type of lingual tonsil cancer? The perspective from a genomic analysis

“…Figure 3B shows the pattern of CPN alteration using a linear graph. The 11q14.1 deletion, where the DLG2 gene (one of the common fragile site genes) is located and which is reported to be associated with oropharyngeal cancer 14 , was frequently observed in both BOT and tonsil cancer. On the other hand, chromosomal amplification in the 7q35 region, where the CNTNAP2 gene (another common fragile site gene) is located 14 , was identified in many cases of oral tongue cancer, but rarely in BOT or tonsil cancer.…”