Nanolock Sensor Detects Cancer Driver Mutation

Researchers have developed an accurate and sensitive “nanolock-nanopore” method that successfully diagnosed a known cancer driver mutation with results at the level of single DNA molecules in tumor tissues of thyroid cancer patients. The method can be adapted to detect a broad spectrum of both transversion and transition mutations, with applications from early diagnostics to individualized targeted therapy and monitoring.

Cancer driver mutations assist in the initiation and progression of cancers, many of which can be stopped in time if caught early enough. The current method for detecting driver mutations is real-time PCR, but it is not accurate enough to detect these genetic changes reliably. Researchers have developed methods to read the genetic sequence by moving it through a nanopore, but also this method is not accurate enough on its own.

Building on their previous work, Prof. Li-Qun Gu, of University of Missouri (Columbia, MO, USA), and colleagues sought a way to better pinpoint these mutations, and with single-molecule resolution. They developed and investigated their novel method using as a test case the known BRAF V600E mutation. The team has now found that mutant DNA carrying a nanolock undergoes a unique type of unzipping when it moves through the nanopore. Detecting this activity resulted in a highly accurate and sensitive nanopore fingerprint for the BRAF mutation in the thyroid cancer patients’ tumor tissue samples.

The researchers anticipate the approach, once integrated with a miniature high-throughput device, could enable PCR-free detection of various disease-causing mutations for diagnosis and prognosis.

The study, by Wang Y et al, was published July 5, 2017, in the journal ACS Sensors.

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