title: Clinicopathological characteristics of RHOA mutations in a Central European gastric cancer cohort.
abstract: Genomically stable gastric cancers (GCs) are enriched for the diffuse phenotype and hotspot mutations of RHOA. Here we aimed to validate the occurrence, phenotype and clinicopathological characteristics of RHOA mutant GCs in an independent Central European GC cohort consisting of 415 patients. The RHOA genotype (exon 2 and 3) was correlated with various genotypic, phenotypic and clinicopathological patient characteristics. Sixteen (3.9%) tumours had a RHOA mutation including four hitherto unreported mutations, that is, p.G17Efs*24, p.V24F, p.T37A and p.L69R. RHOA mutation was more prevalent in women (5.4% vs 2.8%), distal GCs (4.5% vs 2.4%), in poorly differentiated GCs (G3/G4; 4.8% vs 1.1%), T1/T2 tumours (6.2% vs 3.1%) and lacked distant metastases. Nine RHOA mutant GCs had a diffuse, four an intestinal, two an unclassified and one a mixed Laurén phenotype. KRAS and RHOA mutations were mutually exclusive. A single case showed both a RHOA and a PIK3CA mutation. No significant difference was found in the overall survival between RHOA mutant and wildtype GCs. Our study confirms the occurrence and clinicopathological characteristics of RHOA hotspot mutations in an independent patient cohort. However, we found no evidence for a prognostic or growth advantageous effect of RHOA mutations in GC.
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Behrens
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Böger
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Krüger
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D005743:Gastrectomy; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D016283:Proto-Oncogene Proteins p21(ras); D020742:rhoA GTP-Binding Protein; C117307:KRAS protein, human; C066737:RHOA protein, human; C484760:PIK3CA protein, human
keywords: GASTRIC CANCER; GASTRIC PATHOLOGY; GENETICS