CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions.

BACKGROUND: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). METHODS: After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed ß-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. RESULTS: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. CONCLUSIONS: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.

La ginecología natural en América Latina: Un movimiento sociocultural del presente / A ginecologia natural na América Latina: Um movimento sociocultural do presente / The natural gynecology in Latin America: A sociocultural movement of the present

Resumen Este artículo se propone describir algunas de las características de la Ginecología Natural, a partir de la consideración de su desarrollo como expresión sociocultural emergente en la última década en América Latina. Siguiendo los criterios de la teoría fundamentada, se describen dos de las categorías más comunes en una serie de textos escritos y circulados de manera independiente a lo largo del territorio en los últimos cuatro años. Por un lado, el principio informativo y pedagógico, que traza una trama de saberes recuperados y compartidos entre pares. Por el otro, un cuestionamiento constante de la deriva patologizadora y biomedicalizante de la medicina. Los resultados obtenidos permiten esbozar un ideario compartido, pero en constante transformación.

Resumo Este artigo pretende descrever algumas das características da Ginecologia Natural, com base em seu desenvolvimento como expressão sociocultural emergente na América Latina desta última década. Seguindo critérios da teoria fundamentada, são descritas duas das categorias comuns em textos escritos e circulados de maneira independente nesse território, nos últimos quatro anos. Por um lado, o princípio informativo e pedagógico, que mostra um entrelaçamento de saberes recuperados e compartilhados entre pares. Por outro, um questionamento constante da tendência patologizadora e biomedicalizante da medicina. Os resultados obtidos permitem delinear um conjunto de ideias compartilhado e, não obstante, em constante transformação.

Abstract This article tries to describe some of the characteristics of Natural Gynecology, considering its development as a sociocultural expression that emerged in the last decade in Latin America. Following the criteria of the Grounded theory, two of the most common categories in a series of texts written and distributed independently in the last four years are described. On the one hand, the informative and pedagogic principle, combining information brought from ancient knowledge and from the knowledge that is shared among pairs. On the other hand, a constant questioning of the pathologizing and biomedicalizing drift of medicine. The results obtained allow us to sketch a shared ideology, but in permanent transformation.