Sequencing Telomeres In A Snap

Researchers in Singapore have developed a new system for accurate and speedy telomere profiling, which could impact the diagnosis of age-related diseases.

AsianScientist (Sep. 25, 2020) – Researchers in Singapore have developed a method to measure the length of telomeres in under three hours. These findings, published in Science Advances, could speed up the diagnosis of diseases involving abnormal telomeres, such as certain cancers.

Telomeres are repetitive stretches of DNA found at the end of chromosomes. Similar to the plastic tips at the ends of shoelaces which prevent them from fraying, telomeres protect DNA against genome instability, preventing cancers and regulating the aging process. As they shorten each time a cell divides, telomeres can act like a molecular clock, providing vital information about whether a cell is aging normally.

Conventional methods for measuring telomeres are often time-consuming and require skilled operators. These methods also fail to provide precise information on individual telomere lengths and quantities required to accurately diagnose or determine telomere abnormalities.

To get around this problem, a team led by Assistant Professor Cheow Lih Feng of the National University of Singapore combined real-time polymerase chain reaction (RT-PCR) with microfluidics to develop the Single Telomere Absolute-length Rapid (STAR) assay, which allowed them to measure the absolute length of individual telomeres in less than three hours.

The researchers first distributed individual telomere molecules into thousands of tiny chambers in a microfluidic chip. They then performed RT-PCR across all the chambers in a massively parallel manner, using the PCR amplification kinetics as a measure of the telomere length.

To test their invention, the team collaborated with Dr. Amos Loh from KK Women’s and Children’s Hospital (KKH) to validate their assay on cancers linked to the alternative lengthening of telomere (ALT) pathway, namely sarcomas and gliomas, which are cancers of the connective tissue and the brain, respectively. Patients with these cancers tend to have telomeres that are either longer or shorter than usual, as well as extra copies of telomeres, which are associated with a poorer prognosis.

The researchers showed that the STAR assay was effective in diagnosing the ALT status in pediatric neuroblastoma, which can serve as a useful prognosis indicator for this cancer.

“Previously less recognized in patients, telomere abnormalities like ALT have been recently identified to be a new risk marker in neuroblastoma. Since neuroblastoma with telomere abnormalities have poorer outcomes, this new method of measuring telomeres can now facilitate simpler and more rapid identification of ALT in patients to more accurately define their disease prognosis,” said Loh, who is a senior consultant at KKH’s Department of Pediatric Surgery.

“The combination of rapid workflow, scalability and single-molecule resolution makes our system unique in enabling the use of telomere length distribution as a biomarker in disease and population-wide studies,” Cheow added. “It will be particularly useful for diagnosing telomere maintenance mechanisms within clinical time scales, to determine personalized, therapeutic or preventive strategies for patients.”

The team is looking to extend their research and apply the STAR assay platform for use in hospital settings.

The article can be found at: Luo et al. (2020) Massively Parallel Single-molecule Telomere Length Measurement with Digital Real-time PCR.


Source: National University of Singapore.
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