Researchers develop new method that could facilitate cancer diagnosis
Researchers led by the European Molecular Biology Laboratory (EMBL) in Heidelberg and the Centre for Bioinformatics at Saarland University in Saarbrücken, Germany, have developed a cheaper and faster method for checking genetic differences in individual cells. This method outperforms existing techniques in terms of the information received. This new method could become a new standard in research on individual cells, and potentially for clinical diagnosis in the genetics of diseases, including cancer. The results have been published in Nature Biotechnology.
"Our new method for studying genetic variation in individual cells could transform the field of mutation detection," says Ashley Sanders, one of the study's lead authors, who works at EMBL Heidelberg, Germany. The method she and her colleagues have developed, called single cell tri-channel processing (scTRIP), allows them to study genetic variations in the DNA of a single cell and directly measure genetic variations as they form in new cells. Unlike existing methods that could only detect large-scale changes in the genome, scTRIP can detect small-scale changes as well as many types of genetic variation that were invisible with other methods on a single cell.
The researchers tested their method in leukemia cells derived from patients. In their sample, the team found four times as many variants in the patient as were detected by standard clinical diagnostics. Among these variants was a missed clinically relevant translocation that resulted in the overexpression of a cancer gene. They also observed a catastrophic chromosomal rearrangement that had been missed in the initial diagnosis of leukemia. This rearrangement likely occurred when a single chromosome broke and was then restuck in a different order.
"These initial results show that our method significantly outperforms existing methods. Our method is much faster and cheaper than the methods currently used to discover genetic variants in individual cells. This could be very useful for clinical applications," says Tobias Marschall from the Center for Bioinformatics at Saarland University and the Max Planck Institute for Informatics. The team has begun to extend its use of the method to analyse different forms of leukaemia and assess its potential clinical utility.
Since the heterogeneity of a sample can best be studied at the level of a single cell, researchers around the world are working to develop technologies to improve the information received. "While existing techniques show how different cells can behave or respond to manipulation or treatment, research and application have so far focused on measuring RNA within a cell. However, the measurement of DNA in a single cell has so far received much less attention," explains Tobias Marschall. Since it is expected that DNA examination will lead to a better understanding of how these genetic changes lead to different cellular behaviours, the new method meets the needs of researchers and physicians.
The scTRIP project is based on technology that Dr. Ashley Sanders developed during her PhD in Vancouver. "scTRIP combines signals from three distinct information channels within the genomic code of the individual cell," says Jan Korbel, Group Leader at EMBL Heidelberg. "The method allows us to discover the full spectrum of DNA rearrangements in individual cells."
Now, thanks to scTRIP, the researchers are continuing their research on a very fundamental question: To what extent does a cell in the body differ from other cells in the context of cancer as well as from normal cells? Until now, they have not been able to answer this question because they lacked the technology to do so. "Thanks to scTRIP, we can now directly measure the mutation processes that act within cells to generate new genetically distinct populations," says Sanders. As next steps in their research, the team plans to study mutation processes in different types of human cells and assess the implications of these differences for human disease.
