Genomic and genetic alterations influence the progression of gastric cancer

Abstract

Gastric cancer is one of the leading causes of cancer-related deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer. In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.

Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients

“…Epigenetic inactivation of tumor-suppressor genes is a fundamental event in the development of many types of cancers (21,22). Here, we demonstrated that reduced expression of RASSF2 frequently occured in gastric cancer lesions.…”

Prognosis in the Cancer of the Stomach

“…Diffuse type gastric cancer is considered to be de novo cancer, and precursor cells have not yet been identified [47]. In contrast, LOH at chromosome 17p (p53) and mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer, while loss of p27 and gene amplification of Ksam and c-met lead to disease progression and metastatic spread [49].…”

“…Microsatellite instability and p53 mutation, reduced p27 expression, cyclin E overexpression and 6.0kb transcripts of the c-met gene are involved in malignant transformation from precancerous lesions to intestinal-type gastric cancer. In addition, DCC loss, APC mutations, 1q loss of heterozygosity (LOH), p27 loss, reduced expression of tumor growth factor (TGF)β type I receptor and HER2 gene amplification are frequently associated with an advanced stage of intestinal-type gastric carcinoma [49]. Diffuse type gastric cancer is considered to be de novo cancer, and precursor cells have not yet been identified [47].…”

Heat shock protein 22 overexpression is associated with the progression and prognosis in gastric cancer

“…Unfortunately, after a complete resection, the 5-year survival rate remains low [3]. Several studies have shown that various genetic and epigenetic alterations are involved in the course of carcinogenesis and progression of gastric cancer [4][5][6]. However, the molecular mechanism involved in the development of gastric cancer remains unclear.…”