Tumor-specific DNA in plasma of breast cancer patients.

The presence of DNA fragments circulating in cancer patients was described a number of years ago. The mere presence of DNA in the circulation is not indicative of cancer. However, there are reports that apoptosis and necrosis of the cancer cells can increase the levels of circulating DNA. The study of plasma DNA with the detection of genetic abnormalities associated with specific cancers has produced some promising results. Primary cancer often harbors ras or p53 mutations and the detection of these mutations in free circulating DNA could indicate the presence of cancer. Other approaches have included detection of specific losses of heterozygosity (LOH), microsatellite instability (MI) and promoter hyper-methylation. For breast cancer, studies published to date have focused on detecting LOH, MI and methylation of the p16INK4A promoter. Good concordance between alterations in the primary tumor and detection of the same alterations in the circulation has been observed. Also, it is encouraging to note that DNA alterations have been detected in patients with small or even in situ lesions, indicating that circulating tumor DNA is shed early in the disease process. If 'universal' breast-specific DNA alterations can be identified, this approach may hold significant promise for early detection of breast cancer.