Combined loss of CDH1 and downstream regulatory sequences drive early-onset diffuse gastric cancer and increase penetrance of hereditary diffuse gastric cancer.
Celina São JoséJosé Garcia-PelaezMarta FerreiraOscar ArrietaAna AndréNelson MartinsSamantha SolísBraulio Martínez-BenítezMaría Luisa Ordóñez-SánchezMaribel Rodríguez-TorresAnna K SommerIris B A W Te PaskeCarlos CaldasMarc TischkowitzMaria Teresa Tusiénull nullNicoline HoogerbruggeGerman DemidovRicharda M de VoerSteve LaurieCarla OliveiraPublished in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (2023)
In this work, we demonstrated that regulatory elements lying down-stream of CDH1 are part of a chromatin network that control CDH1 expression and influence cell transcriptome and associated signalling pathways, likely explaining high disease penetrance and very young cancer-onset. This study highlights the importance of incorporating scientific-technological updates and clinical guidelines in routine diagnosis, given their impact in timely genetic diagnosis and disease prevention.