Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer

• DOI: 10.1126/science.aao3130
• Publication Date: 2017-09-15T01:10:32Z
• Authors: Jarno Drost; Ruben van Boxtel; Francis Blokzijl; Tomohiro Mizutani; Nobuo Sasaki; Valentina Sasselli; Joep de Ligt; Sam Behjati; Judith E. Grolleman; Tom van Wezel; Serena Nik-Zainal; Roland P. Kuiper; Edwin Cuppen; Hans Clevers
• Keywords: Organoid

A signature event for organoids Human cancer genomes harbor cryptic mutational signatures that represent the cumulative effects of DNA damage and defects in repair processes. Knowledge how specific originate could have a major impact on diagnosis prevention. One approach to address this question is reproduce experimental systems by genetic engineering then match those found naturally occurring cancers. Drost et al. used CRISPR-Cas9 delete certain enzymes from human colon organoids. In proof-of-concept study, they show deficiency base excision responsible previously identified genome sequencing projects. Science , issue p. 234