INK4/ARF and gastric carcinogenesis

Gastric cancer (GC) is an aggressive disease, with a huge impact on global health, as it still remains the fourth most common type of cancer and the second leading cause of cancer-related death worldwide. Genetic abnormalities involved in the pathogenesis and progression of gastric carcinoma were identified, some of them also correlated with prognosis. Among these genetic abnormalities, the loss-of-function of genes encoded by INK4-ARF locus frequently occurs in cancers. This locus is located on the human chromosome 9p21, spans approximately 35 kilobases and encodes five types of tumor suppressor genes, being the most studied p16 INK4A , p15 INK4B and p14 ARF . Among the several types of INK4/ARF molecular inactivation, one can highlight genetic abnormalities, such as genomic/chromossomic instabilities and microsatellites, mutations and polymorphisms and DNA methylation. In this review we will discuss the main types of molecular alterations on INK4/ARF described on GC.