Search

We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAMdel iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter. This was associated with loss of MSH2 expression, increased mutational burden, MMRD signatures and MS-indel accumulation, the hallmarks of MMRD. In contrast, maturation into brain organoids and examination of blood and fibroblasts failed to show similar processes, preserving MMR proficiency. The combined use of iPSC, organoid technologies and functional genomics analyses highlights the potential of cutting-edge cellular and molecular analysis techniques to define processes controlling tumorigenesis and uncovers a new paradigm of tissue-specific MMRD, which affects the clinical management of these patients. [ABSTRACT FROM AUTHOR]

Due to advancements in technology such as data science and artificial intelligence, healthcare research has gained momentum and is generating new findings and predictions on abnormalities leading to the diagnosis of diseases or disorders in human beings. On one hand, the extensive application of data science to healthcare research is progressing faster, while on the other hand, the ethical concerns and adjoining risks and legal hurdles those data scientists may face in the future slow down the progression of healthcare research. Simply put, the application of data science to ethically guided healthcare research appears to be a dream come true. Hence, in this paper, we discuss the current practices, challenges, and limitations of the data collection process during medical image analysis (MIA) conducted as part of healthcare research and propose an ethical data collection framework to guide data scientists to address the possible ethical concerns before commencing data analytics over a medical dataset., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© National University of Singapore and Springer Nature Singapore Pte Ltd. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)