In EMBO Molecular Medicine, IRB Barcelona scientists at PCB report a technique based on a combination of CRISPR/Cas9 genome editing and patient-derived tumour organoids that allows the study of cell heterogeneity in human tumours.The novel approach was used to examine the behaviour of colorectal cancer stem cells by tracing specific marker genes.

An innovative methodology proposed by researchers with the Colorectal Cancer Laboratory at IRB Barcelona opens up the possibility to study human tumours by means of tracing genetic modifications. Such an approach had previously been feasible only in animal models and it may have broad applicability for the analysis of cancer cell diversity during human tumour development in vitro or after transplantation of tumours to a recipient animal.

“There is a large interest to study how distinct tumour cell population contribute to the evolution of the disease. Until know, these studies have necessary involved experiments of tumour dissociation and cell isolation, which have raised many conceptual and technical caveats. In essence, this new approach brings the power of mouse genetic tools to study human cancer and overcomes the limitations of identifying and tracking tumour cell populations in an intact environment,” explains ICREA Research Professor Eduard Batlle, who led the study published today in EMBO Molecular Medicine.

The researchers combine two novel methodologies, namely patient-derived tumour organoids (an organoid is a miniaturized and simplified version of an organ that is produced in vitro in three dimensions and that shows realistic micro-anatomy), and CRISPR/Cas9 genome-editing techniques (which allow the introduction of markers into genes of interest). The scientists consider that the combined method proved “particularly well suited” for analysing the diversity of cell populations within cancers as it allows the labelling and tracing of distinct tumour cells through desired marker genes.

“For the first time we can analyse cell lineage relationships in growing tumours, and this technique will help us to address how distinct cell populations contribute to growth, dissemination, and resistance to therapy,” wrote the IRB Barcelona authors in reference to the impact expected.
 

• For further information: IRB Barcelona website  [+]

• Reference article : Carme Cortina, Gemma Turon, Diana Stork, Xavier Hernando-Momblona, Marta Sevillano, Mònica Aguilera, Sébastien Tosi, Anna Merlos-Suárez, Camille Stephan-Otto Attolini, Elena Sancho & Eduard Batlle. A genome editing approach to study cancer stem cells in human tumors. EMBO Molecular Medicine (2017). DOI:10.15252/emmm.201707550