Multi-Omic Technology Helps Identify Rare Brain Tumor Cell Subpopulation

Researchers at the Hong Kong University of Science and Technology (HKUST) have developed a new technology that simultaneously performs genomic DNA and RNA sequencing in single cells of both frozen and fresh tissues. This breakthrough will help further cancer research for some of the most complex and rare tumors, opening new doors for drug target discovery.

Existing technologies have limited applicability to simultaneously perform DNA and RNA sequencing in single cells from frozen biobanked tissues; however, this is where most readily available clinical cancer samples can be found.

The team, led by Prof. Angela WU, developed a new versatile single-cell multi-omic profiling technology, scONE-seq, which can analyze frozen cells and difficult-to-obtain cell types, such as bone and brain. This new method can simultaneously collect genomic and transcriptomic information in a tumor through a one-pot reaction, providing crucial information on the tumor's genomic and molecular composition and cellular heterogeneity.

Astrocytoma is an aggressive type of brain tumor with a low five-year survival rate of only around 5 percent. Using scONE-seq, the team discovered a small and unique tumor cell subpopulation in a patient's astrocytoma sample that disguised themselves as normal astrocytes of the brain, which could escape detection using other common tumor sequencing methods. This "spy" tumor cell also showed molecular features related to drug resistance, making it an important direction for future investigations of this disease and possible drug targets.

This study was done in collaboration with clinicians at the Chinese University of Hong Kong and Prince of Wales Hospital and has recently been published in Science Advances. The new technology, scONE-seq, offers a unique perspective on tumor cellular heterogeneity, making it easier to perform larger-scale clinical multi-omics single-cell studies on existing biobanked samples. The application of scONE-seq on frozen tumor tissue led to an integrated investigation of astrocytoma's genotypic and molecular phenotypic heterogeneity, revealing and characterizing differentiated tumor clones.

Prof. Angela WU explains that the scONE-seq approach represents a new path to discovering drug targets and the development of new drugs. "By identifying rare tumor cells which might be missed by previous approaches and result in failure to respond to therapy, we plan to continue our work, using scONE-seq to profile a larger patient cohort, and hope to have more clinically translational outcomes in the future."