Methylated DNA Blood Test Monitors Breast Cancer Progress and Treatment Response

An advanced assay that measures DNA hypermethylatation in blood samples can diagnose advanced breast cancer, as well as monitor tumor burden and treatment response in women with metastatic breast tumors.

The cMethDNA assay developed by investigators at John Hopkins University (Baltimore, MD, USA) is a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers. These genes were selected by analyzing DNA methylation patterns in breast tissue (103 cancer, 21 normal) with the Illumina (San Diego, CA, USA) Infinium HumanMethylation27 Beadchip assay.


The 10-gene panel was validated using information from The Cancer Genome Atlas Project (Bethesda, MD, USA) breast cancer methylome database. The Cancer Genome Atlas Project is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

The investigators evaluated the assay's ability to detect methylated tumor DNA in 52 blood samples—24 from patients with recurrent stage IV breast cancer and 28 from healthy women without breast cancer, and again in blood samples from 60 individuals—33 from women with all stages of breast cancer and 27 from healthy women. In both studies the blood test distinguished the patients with metastatic breast cancer from healthy women with accuracy up to 95%.

In a separate pilot study of 29 patients receiving drug treatment, the cMethDNA assay faithfully reflected patient response to chemotherapy.

"The goal is to develop a test that could be administered routinely to alert the physician and patient as soon as possible of a return of the original cancer in a distant spot. With the development of cMethDNA, we have taken a first big step toward achieving this goal," said senior author Dr. Saraswati Sukumar, professor of oncology at Johns Hopkins University. "Our assay shows great potential for development as a clinical laboratory test for monitoring therapy and disease progression and recurrence. If it is determined early that a treatment is not working, clinicians can save time and switch to a different therapy."

Results obtained with the cMethDNA assay were published in the April 15, 2014, issue of the journal Cancer Research.

Related Links:
John Hopkins University
Illumina
The Cancer Genome Atlas Project