GC is an asymptomatic disease at early stages and is therefore often detected late; the 5-year survival being only 20–30% [2]. As treatment modalities are limited, new approaches for diagnosis

and treatment are necessary. This review focuses on recent discoveries by using next-generation sequencing and novel insights in the field of microRNA biology in GC. Two studies recently identified frequent somatic mutations in the ARID1A gene in GC applying exome sequencing [3, 4]. At the same time, Jones et al., [5] applied Sanger sequencing to test for alterations of ARID1A in several neoplasms, among them were 100 gastric carcinomas. The protein encoded by ARID1A (Arid1A, also called BAF250a, SMARCF1, or OSA1) is a accessory subunit of the SWI-SNF chromatin learn more remodeling complex that is involved in processes of DNA repair, differentiation, development, and has a regulatory role in proliferation [6]. Mutations were identified in 8–10% of the gastric tumors (unsorted material, including all classifications and all microsatellite statuses) [4, 5] and in 11% of the microsatellite stable GC that were not infected with Epstein-Barr virus [3]. Notably, cancers with Epstein-Barr virus infection

showed mutations of ARID1A in 73% of the cases, and all studies noted a high mutation rate from 44 to 83% of GC with microsatellite instability [3-5]. Additionally, ARID1A mutations this website were negatively associated with mutations in TP53 [3] and occurred together with PIK3CA mutations [4]. Overexpression of Arid1A in tissue culture conditions led to reduced proliferation of GC cells, and silencing of Arid1A led to increased proliferation and to increased levels of the transcription factor E2F1 and cyclin

E1, both important players buy Metformin in cell cycle regulation [4]. Interestingly, GC cases with Arid1A alterations (gene mutation or protein deficiency) had predicted a longer recurrence-free survival in a multivariate analysis, and the authors suggested that these cancers belong to a molecular subgroup with distinct carcinogenic mechanisms as well as clinical behavior [3]. MicroRNAs (miRNA) are short non-coding RNAs with a length of approximately 22 nucleotides. Binding of their target mRNA results in repression of translation or initiation of mRNA degradation. The mechanism of action is most likely dependent on the miRNA–mRNA complementarity, with perfect alignment leading to mRNA cleavage, and binding with mismatches leading to inhibition of mRNA translation [7]. Dysregulated miRNAs are frequent in GC, and they target cellular processes involved in proliferation, invasion, and metastasis, and resistance to apoptosis [8]. In the search for miRNAs as biomarkers in GC, Konishi et al. [9] performed a microarray analysis where they compared the circulating miRNA levels in pre- and postoperative plasma.