Kasper Karlsson, Moritz J Przybilla, Eran Kotler, Aziz Khan, Hang Xu, Kremena Karagyozova, Alexandra Sockell, Wing H Wong, Katherine Liu, Amanda Mah, Yuan-Hung Lo, Bingxin Lu, Kathleen E Houlahan, Zhicheng Ma, Carlos J Suarez, Chris P Barnes, Calvin J Kuo, Christina Curtis
The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1 . Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2 years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders...
May 31, 2023: Nature