DNA Palindromes as a Novel Tumor Marker in Extracellular Vesicles from Liquid Biopsy
Abstract
The goal of our project is to prevent overdiagnosis and overtreatment of breast cancer by developing a sensitive blood test. Our assay is designed to capture a trace of cancer in patients’ blood. Breast cancer is diverse in character. Some of the tumors grow very slowly and never cause any harm or requiring treatment. Other tumors are very aggressive and grow very fast to spread in a body. Mammography can catch both types of tumors. Twenty to thirty percent of tumors diagnosed by mammography are restricted, very slow growing tumors called ductal carcinoma in situ (DCIS) or stage zero tumors. The vast majority (>85%) of these tumors will never develop into aggressive ones in a woman’s lifetime. Thus, the majority of DCIS is not harmful. The problem is that mammography alone cannot tell one type from the other. As a result, all the tumors diagnosed by mammography are treated similarly: biopsy, surgery, chemotherapy, hormone therapy, and radiation therapy. These treatments can cause both immediate effects (breast removal, pain, and scarring, hair loss, nausea, skin burns, etc.) and long-term effects (heart disease, infertility, and secondary cancers). These treatments should be avoided if tumors are not harmful. Thus, there is a strong need to find out which tumors are harmful and require intensive treatment. When breast tumors become aggressive, tumors invade nearby vessels to leave the trace of tumor DNA in blood. Tumor DNA in blood is a sign of aggressive tumors. However, detecting tumor DNA in blood is not a straightforward task because blood contains normal DNA from other parts of the body, not just cancer. In some cases, tumor DNA from cancer represents less than 0.1% of all blood DNA. The situation is even worse for very early-stage tumors, which makes the detection of tumor DNA in blood a search for “a needle in a haystack.” We will overcome this problem using the method we developed. The advantage of our method is that we can eliminate normal DNA from samples and amplify tumor DNA, which makes our approach extremely sensitive. No other approach can eliminate normal DNA in blood. Our method has been validated in breast tumor tissues but hasn’t been tested in patients’ blood. Therefore, in this application, we will first apply this method to the blood samples from both early- and late-stage patients that are stored at Cedars-Sinai Medical Center. Finally, we will test blood samples from women with suspicious signs in mammography.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810058
Entities
People
- Hisashi Tanaka
Organizations
- Cedars-Sinai Medical Center
- United States Army