Molecular characterization of gastric cancers: genetic mutations, global DNA methylation and presence of cancer-related pathogens

Gastric cancer is the fifth-most prevalent cancer and the third leading cause of cancer death
worldwide. It is caused by the accumulation of genetic and epigenetic alterations, leading to an
aberrant transcriptional profile that is ultimately responsible for the malignant characteristics of cancer
cells. Several environmental factors increase the risk of gastric cancer, by promoting the occurrence
of those alterations. Among these environmental factors, high-risk gastritis produced by H. pylori
infection is known to be an extremely important risk factor, involved in more than half of the gastric
cancers. Infection with Epstein-Barr virus is also known to be involved in gastric cancer development,
even less frequently than H. pylori infection.
Gastric cancer is a heterogeneous disease, with substantial molecular, genetic and phenotypic
differences among tumours. In the clinical setting, gastric tumours have been typically classified
according to their histological features. More recently, novel classification systems based on their
molecular characteristics have been developed to be combined with previous histological
classification systems. These molecular classifications offer improved accuracy in diagnosis and
prognosis, being crucial for the future implementation of precision medicine, where treatment
selection is based on the molecular characteristics of the tumour rather than its morphological
features.
In this study, I have characterized genetic alterations (mutations) in several cancer-related genes,
epigenetic alterations (genome-wide demethylation) and the presence of H. pylori in a collection of
22 gastric cancer samples, using a variety of PCR-based molecular biology techniques some of which
were previously established in the laboratory. In addition, I have set up the experimental conditions
to analyse the two main mutational hotspots of the PIK3CA oncogene, and attempted a novel qPCR-
based assay to detect the presence of Epstein-Barr virus in gastric samples.
My results revealed an association of genome-wide demethylation with African-American individuals
and TP53 mutations. No other statistically significant associations between the genome-wide
demethylation level and clinicopathological, genetic or epigenetic characteristics were found,
probably due to the limited number of analysed samples.