Whole genome sequencing of colon organoid cultures with artificially induced oncogenic mutations

Using the CRISPR-Cas9 genome editing system, various oncogenic mutations were introduced in the genome of normal adult stem cells derived from the colon. The resulting clonal cultures were subjected to whole genome sequencing. In addition, the cultures were transplanted in a mouse and the resulting primary and metastatic tumors were also subjected to whole genome sequencing. The initial bulk culture, which was used to generate the mutations, was also whole genome sequenced and served as a reference sample to filter germline variants.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 3 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001002719	This dataset contains whole-genome sequencing data files from colon organoid cultures, which were mutated using CRISPR-Cas9 for specific genes (APC, KRAS, TP53 and SMAD4) to generate in vitro transformed cancer cells. After introducing each mutation, the resulting cultures were subjected to whole-genome sequencing. In addition, some cultures were xenotransplanted in recipient mice. The resulting primary tumors and corresponding metastases were subjected to whole-genome sequencing.	HiSeq X Ten	30

Publications	Citations
The somatic POLE P286R mutation defines a unique subclass of colorectal cancer featuring hypermutation, representing a potential genomic biomarker for immunotherapy. Ahn SM, Ansari AA, Kim J, Kim D, Chun SM, Kim J, Kim TW, Park I, Yu CS, Jang SJ. Oncotarget 7: 2016 68638-68649	40
Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids. Fumagalli A, Drost J, Suijkerbuijk SJ, van Boxtel R, de Ligt J, Offerhaus GJ, Begthel H, Beerling E, Tan EH, Sansom OJ, Cuppen E, Clevers H, van Rheenen J. Proc Natl Acad Sci U S A 114: 2017 E2357-E2364	144
Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer. Drost J, van Boxtel R, Blokzijl F, Mizutani T, Sasaki N, Sasselli V, de Ligt J, Behjati S, Grolleman JE, van Wezel T, Nik-Zainal S, Kuiper RP, Cuppen E, Clevers H. Science 358: 2017 234-238	223