Mutational Signatures in Gastric Cancer and Their Clinical Implications

SIMPLE SUMMARY: There is a lack of molecular biomarkers that would allow better characterisation and categorisation of gastric tumours. Distinct mutational patterns have been observed at both the whole genome and exome levels and have been referred to as mutational signatures. Some of these characteristic mutational patterns have been associated with defects in DNA repair mechanisms or linked to exogenous mutagens. The mutational signatures found in gastric tumours could be used as prognostic biomarkers and could provide new information about the drivers of gastric carcinogenesis, which might be useful for the improvement in disease treatment options. This review summarises mutational signatures found in gastric cancer and their clinical potential. ABSTRACT: Gastric cancer is characterised by high inter- and intratumour heterogeneity. The majority of patients are older than 65 years and the global burden of this disease is increasing due to the aging of the population. The disease is usually diagnosed at advanced stages, which is a consequence of nonspecific symptoms. Few improvements have been made at the level of noninvasive molecular diagnosis of sporadic gastric cancer, and therefore the mortality rate remains high. A new field of mutational signatures has emerged in the past decade with advances in the genome sequencing technology. These distinct mutational patterns in the genome, caused by exogenous and endogenous mutational processes, can be associated with tumour aetiology and disease progression, and could provide novel perception on the treatment possibilities. This review assesses the mutational signatures found in gastric cancer and summarises their potential for use in clinical setting as diagnostic or prognostic biomarkers. Associated treatment options and biomarkers already implemented in clinical use are discussed, together with those that are still being explored or are in clinical studies.