Journal d'épigénétique clinique Libre accès

Abstrait

Alterations of DNA methylation seem to be an early event in the development of tumors from the upper aero digestive tract

Sheila Coelho Soares Lima Brazilian National Cancer Institute–INCA, Brazil

Extended Abstract
Introduction:
Statement of the Problem: Tumors from the upper aerodigestive tract (UADT) rank among the 10 most frequent
neoplasias worldwide. These tumors are more prevalent in developing countries, arising from a squamous epithelium
and are usually associated with tobacco, alcohol consumption and HPV infection. The most common histological type
is squamous cell carcinoma and the most commonly affected sub sites include larynx, oral cavity, pharynx and
esophagus. Although they share similarities, UADT cancer comprises a group of neoplasias with high clinical and
phenotypic heterogeneity and inspite of the recent advances in the identification of biomarkers and new therapeutic
targets, no significant gains in overall survival have been observed. Between the associated causes, the development of
second primary tumors in the UADT stands out. It is hypothesized that the squamous epithelium lining the affected
organs goes through a process known as cancerization field, in which different morphologically normal areas acquire
molecular alterations, making them prone to become neoplastic. Based on this, we have been interested in
understanding the epigenetic mechanisms that lead to the development of each of these tumors. Methodology &
Theoretical Orientation: Microarrays have been used to determine the DNA methylation signature of UADT tumors
with further validation by pyro-sequencing in independent samples.
Findings: Interestingly, we showed that each subtype of UADT cancer carries a specific DNA methylation signature.
They differ in terms of hyper/hypomethylation frequency; affected genomic regions, genes and pathways and
transcription factor networks. We have also shown that aberrant DNA methylation of genes involved in epithelium
protection and in apoptosis control is an early event in the development of UADT tumors. Therefore, our data indicates
that these neoplasias show an epigenetic convergence with respect to early changes, but also diverge in terms of
carcinogenic pathways, which may have an impact on prognosis and response to therapy
Recent Publications1. Degli Esposti D, et al. (2017) Unique DNA methylation signature in HPV-positive head and
neck squamous cell carcinomas. Genome Medicine 9:33. 2. Herceg Z, et al. (2017) Roadmap for investigating
epigenome deregulation and environmental origins of cancer. International Journal of Cancer 142(5): 874-882. 3.
Gonzaga I M, et al. (2017) TFF1 hypermethylation and decreased expression in esophageal squamous cell carcinoma
and histologically normal tumor surrounding esophageal cells. Clinical Epigenetics 9:130. 4. Lima S, et al. (2011)
Identification of a DNA methylome signature of esophageal squamous cell carcinoma and potential epigenetic
biomarkers. Epigenetics 6(10):1217-1227.