Many cancers can be stopped in their tracks if caught early enough.The moment when healthy cells turn into cancer cells is a critical point.
‘A nanolock is a special structure that can stabilize base pairs of the DNA at the mutation site as it goes through a nanopore.’
Cancer driver mutations assist in the initiation and progression of cancer. One such mutation in the BRAF gene has been associated with numerous cancers, including thyroid cancer. The current method for detecting driver mutations is real-time PCR, in which mutant DNA sequences are selectively amplified and copied, 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 again, the method is not nearly accurate enough on its own. So, Li-Qun Gu and colleagues sought a way to better pinpoint these mutations, and with single-molecule resolution, building on their previous work developing a “nanolock-nanopore” sensor.
The team has now found that mutant DNA carrying a nanolock undergoes a unique type of unzipping when it moves through the pore. Detecting this activity resulted in a highly accurate and sensitive nanopore fingerprint for the BRAF mutation in thyroid cancer patient tissue samples. The researchers say that they anticipate the approach, once integrated with a miniature, high-throughput device, could enable accurate and PCR-free detection of various disease-causing mutations for diagnosis and prognosis.