Quick liquid biopsy
Researchers from The Kimmel Cancer Center at Johns Hopkins University has created a test that allows to reliably determine the presence of cancer DNA in the blood of patients with metastatic breast cancer within five hours. So far, this is only a prototype for research purposes, but potentially it can replenish the diagnostic arsenal of oncologists to quickly determine the effectiveness of cancer treatment.
Liquid Biopsy for Breast Cancer Methylation (LBx-BCM) is compatible with the commercially available GeneXpert® molecular testing platform and can detect methylation – a type of epigenetic label – in one or more of the nine genes (AKR1B1, TM6SF1, ZNF671, TMEFF2, COL6A2, HIST1H3C, RASGRF2, HOXB4 and RASSF1), which change in breast cancer, in 4.5 hours. The laboratory assistant will practically spend less than 15 minutes on this.
Breast cancer often does not respond to chemotherapy, but several courses of treatment are taken before oncologists can conduct imaging studies and determine whether the treatment is effective. The fact is that visualization can be useful for detecting changes in large tumors, but practically does not determine changes in smaller neoplasms.
The aim of the researchers was to develop an analysis that would be easy to perform and could be used in hospitals to evaluate the effectiveness of therapy and timely make changes in the management tactics of patients with metastatic breast cancer.
Using the LBx-BCM test, developed in collaboration with scientists from Cephied, is simple: the laboratory technician must place a sample of the patient's blood or plasma in a test tube containing a mixture for DNA extraction and immerse the contents in a GeneXpert system cartridge. Chemical modification and amplification of methylated DNA takes place in it, which is then captured, and the device gives the result. The test identifies methylation markers in nine genes that characterize four subtypes of breast cancer.
The group has previously developed a liquid biopsy technique called cMethDNA, which detects hypermethylation in 10 genes that change in breast cancer. Hypermethylation is an epigenetic DNA change that often suppresses the function of genes that inhibit the unrestrained growth of cancer cells. Hypermethylation of DNA circulating in the blood indicates a recurrence or metastasis of cancer. This test can identify up to 90% of patients with metastatic breast cancer and predict the response to therapy and long-term treatment results. However, it takes 10 days to complete and requires a high degree of technical competence. The LBx-BCM test is automated and takes much less time.
To assess the accuracy of LBx-BCM, the researchers first asked two laboratory assistants to perform the test on different days, using samples from 11 patients with metastatic breast cancer and four without it. The results were the same in more than 90% of cases. The researchers also tested the test's ability to detect metastatic breast cancer in two sets of samples from previous studies conducted at Johns Hopkins University. They determined the methylation of nine genes in 20 serum samples from patients with metastatic breast cancer and 20 from healthy volunteers. The second set included samples from 40 people with metastatic breast cancer, 17 with benign breast diseases and 9 without breast cancer. In both sets, LBx-BCM found 2-200 times more methylated DNA in the blood plasma samples of breast cancer patients than in healthy samples or in benign tumors. In experiments, the test correctly detected cancer in 83% of cases and correctly excluded cancer in 92% of cases, with an overall diagnostic accuracy of 85%.
Further prospective clinical studies will assess the sensitivity of LBx-BCM and its effectiveness for control during the treatment of metastatic breast cancer.
Article M.Jo Fackler et al. The development of an Automated Liquid Biopsy Assay for Methylated Markers in Advanced Breast Cancer is published in the journal Cancer Research Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Johns Hopkins Medicine: Liquid Biopsy Detects DNA Markers in Advanced Breast Cancer Within Five Hours.