Researchers at the Hong Kong University of Science and Technology (HKUST) have developed a novel technology for simultaneous genomic DNA and RNA sequencing in single cells from frozen and fresh tissues and identified rare brain tumor cell “spies” disguised as normal cells using this method.
This breakthrough advances cancer research for some of the most complex and rare tumors, opening new directions for future drug target discovery.
Genomic DNA and RNA sequencing are crucial for determining the cancer treatment, as it offers important information about tumor genomic and molecular composition, or cellular heterogeneity, which influences the disease pathology as well as the tumor’s ability to develop drug resistance.
Our current understanding of cancer does not fully explain why tumors relapse or become resistant to treatment, and research data obtained from DNA and RNA sequencing simultaneously may be able to unravel the mysteries of cancer such as tumor relapse and drug resistance.
However, existing techniques have limited applicability for the simultaneous DNA and RNA sequencing of single cells from frozen biobank tissues, which constitute the majority of readily available clinical cancer samples.
The research team, led by Prof. Angela Wu, associate professor of HKUST’s Division of Life Science and Department of Chemical and Biological Engineering, developed a new versatile single-cell multi-omic analysis technology called scONE-seq, which can analyze frozen cells and hard-to-obtain cell types like bone and brain. This new method also greatly simplifies the simultaneous collection of genomic and transcriptomic information in tumor cells.
Astrocytoma is a deadly and aggressive brain tumor, with only about five percent of patients living with it five years after diagnosis. Using their novel single-cell technology, the HKUST research team discovered a small but distinct subpopulation of tumor cells in a patient’s astrocytoma sample.
This unique population of tumors disguised themselves as the brain’s normal astrocytes and could evade detection using other common tumor sequencing methods. In addition, this “spy” tumor cell also exhibits molecular features associated with drug resistance.
The team noted that the comprehensive role of this “spy” tumor cell in tumor progression will be an important direction for future studies of this disease and possible drug targets.
Wu said, “By identifying rare tumor cells which might be missed by previous approaches and result in failure to respond to therapy, the scONE-seq approach represents a new path to discovering drug targets and the development of new drugs. 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.”
The research was published in Sciences Advances on Jan. 4, 2023.