English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

RHOA, Ras homolog gene family member A, encoding a small GTPase, is a novel and contentious cancer driver gene. In 2014, frequent somatic RHOA mutation was identified almost exclusively in diffuse-type gastric cancer (DGC) in three studies [1–3]. Kakiuchi et al. [1] and The Cancer Genome Atlas (TCGA) Research Network [2] indicated gain-of-function mutations of RHOA. On the other hand, Wang et al. [3] indicated loss-of-function mutations of RHOA. This potential discrepancy attracted great attention from many investigators, including those who enthusiastically focus on RHOA as a potential therapeutic target. Historically, although increased RHOA expression was frequently observed in various cancers and was suggested to be associated with disease progression and poor prognosis, RHOAmutation was uncommon [4]. In this issue of Gastric Cancer, Ushiku et al. [5] report clinicopathological characteristics of RHOA-mutated DGCs for the first time [5]. Ushiku et al. analyzed 87 DGCs, 22 RHOA-mutated DGCs and 65 RHOA wild-type (RHOA-wt) DGCs, for their histopathological and clinical characteristics, especially focusing on heterogeneity of histological features and growth patterns of DGCs. RHOA-mutated DGCs more frequently contained focal tubular differentiation in their intramucosal areas than RHOA-wt DGCs. Notably, RHOAmutated DGCs were significantly inclined to spread laterally in the mucosae with infiltration between normal gastric glands without well-circumscribed margins (permeative growth), resulting in a lower ratio of deeply invasive components to mucosal components in RHOA-mutated DGCs than in RHOA-wt DGCs. In previous studies [1, 3], RHOA mutations were detected both in intramucosal regions and in invasive regions and also both in diffuse components and in tubular components, and were considered to occur in the early phase of carcinogenesis. From these findings taken together, it was suggested that intestinal-type intramucosal gastric cancer possibly develops into DGC through stepwise progression in the presence of a RHOA mutation. Ushiku et al. also investigated the clinical impact of RHOA mutation on patient survival, but they did not observe significant differences. However, they discuss the possibility that RHOA deregulation could be still significantly associated with patient survival for the following reasons. First, this study consisted of a small cohort; therefore, a larger cohort would be required to determine the prognostic significance of RHOA mutation. Second, the heterogeneity in the cohort might have influenced the result of the analysis. The cohort included five patients with This comment refers to the article available at doi:10.1007/s10120015-0493-0.

RHOA mutation may be associated with diffuse-type gastric cancer progression, but is it gain or loss?