Gene-based blood tests can detect more skin cancers

Genetic testing of tumour and blood fluid samples in skin cancer patients has shown that two new blood tests can reliably detect previously unidentifiable forms of the disease. The blood tests, which take only 48 hours, were developed by researchers at NYU Langone Medical Center in conjunction with Bio-Rad Laboratories.

The researchers say the new tools are the first to identify melanoma DNA in the blood of patients whose cancer is spreading and who lack defects in either the BRAF or NRAS genes, already known to drive cancer growth. Their study was recently presented at the annual meeting of the American Association for Cancer Research by senior investigator David Polsky.

Polsky explained that the tests monitor blood levels of DNA fragments, known as circulating tumour DNA (ctDNA), that are released into the blood when tumour cells die and break apart. Specifically, the test detects evidence of changes in the chemical building blocks (or mutations) of a gene that controls telomerase reverse transcriptase (TERT), a protein that helps cancer cells maintain the physical structure of their chromosomes.

Polsky said the detected changes occur in mutant building blocks, in which a cytidine molecule in the on-off switch for the TERT gene is replaced by another building block, called thymidine. Either mutation, C228T or C250T, results in the switch being stuck in the ‘on’ position, helping tumour cells to multiply.

The study saw researchers check the new tests against 10 tumour samples taken from patients diagnosed with and without metastatic melanoma, as well as four blood plasma samples. Blood test results matched correctly in all cases known to be either positive or negative for metastatic melanoma. Successful detection occurred for samples with as little as 1% of mutated ctDNA in a typical blood plasma sample of 5 mL. TERT mutations were absent in tests of normal blood plasma and tonsil tissue.

Polsky said the blood tests have advantages over current methods for monitoring the disease because they avoid the radiation exposure that comes with CT scans and can be performed more easily and more often. He and his fellow researchers added that having quick and accurate monitoring tools for all types of metastatic melanoma may make it easier for physicians to detect early signs of cancer recurrence.

Once clinically validated, Polsky expects the Bio-Rad tests to quickly gain widespread use, with his previous research finding that similar blood tests for BRAF and NRAS mutations worked better in identifying new tumour growth than existing blood tests for the protein lactate dehydrogenase. This is because lactate dehydrogenase levels may spike during aggressive tumour growth but can also rise as a result of other diseases and biological functions.

He said further studies of the new blood tests will be used to gauge their use in monitoring progression of aggressive cancer, in order to more quickly determine when switching to an alternative therapy is warranted, and to detect other types of cancer, such as brain tumours, that also have TERT mutations.

Image courtesy of Dean Hochman under CC BY 2.0