Novel RNA sequencing technology to investigate gene activities and mutations in cancer cells


Scientists from Agency for Science, Technology and Research’s (A*STAR) Genome Institute of Singapore (GIS), the National Cancer Centre Singapore (NCCS) and Fluidigm Corporation have developed a new technology to simultaneously and systematically investigate individual cancer cells within a tumour. The study was published in Clinical Chemistry on 7 December 2018.

It has been established that not every cancer cell in a tumour is alike (also known as clonal heterogeneity), and that mutations develop in the cells during the course of tumour growth. Some of these mutations can cause the tumour to evolve and develop resistance against therapy. To understand the complexity of this process, it is therefore often necessary to sequence the entire tumour.

However, there are limitations to existing technologies that illuminate the different components of a tumour, and how such mutations change its characteristics. In particular, it is technically challenging to simultaneously sequence a single cell’s DNA and analyse the activities of genes.

To address this problem, the team headed by Dr Axel Hillmer, Group Leader at GIS and senior author of this study, developed a novel technology termed COncurrent single cell RNA and TArgeted DNA sequencing (CORTAD-seq) – on an automated Fluidigm C1 microfluidic platform. CORTAD-seq allows researchers to test for the presence of mutations in single cells with high accuracy and take snapshots of the gene activities within those cells.

Dr Kong Say Li, Research Associate at GIS and lead author of this study, said, “CORTAD-seq is a tool which can be implemented easily by other researchers, and lead to more impactful discoveries. This method allows for insights into cancer evolution and clonal heterogeneity, the mechanisms of drug resistance towards targeted therapy, as well as the difference in gene activities of cancer and normal cells through the identification of cancer mutations.”

Dr Mark Lynch, Director of Single-Cell Genomics at Fluidigm, said, “Fluidigm is privileged to be partnered with GIS to develop CORTAD-seq, using microfluidics on the C1 system. This novel single-cell, multi-omic technology will help the characterisation of the tumour microenvironment at single-cell resolution and will thus help studies in cancer and immuno-oncology.”

Professor Ng Huck Hui, Executive Director at GIS, said, “We are delighted to be working with NCCS and Fluidigm Corporation to develop this novel technology. Such cross-boundary collaborations allow us to further our capabilities and break new frontiers in genomic science. Doing so will also help us better understand how cancer works, and will help bring about better healthcare outcomes for Singaporeans.”

Source – Genome Institute of Singapore 

Kong SL, Li H, Tai JA, Courtois ET, Poh HM, Lau DP, Haw YX, Iyer NG, Tan DSW, Prabhakar S, Ruff D, Hillmer AM. (2019) Concurrent Single-Cell RNA and Targeted DNA Sequencing on an Automated Platform for Comeasurement of Genomic and Transcriptomic Signatures. Clin Chem 65(2):272-281. [abstract]

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