Tumor Specific Genetic Fingerprints in the Peripheral Blood of Women with Breast Cancer

摘要

The importance of DNA abnormalities to tumorigenesis is not in doubt but their clinical utility has not yet been fully elucidated. We performed a pilot study to evaluate detection of occult circulating tumor DNA using tumor- specific microsatellite alterations in subjects previously diagnosed with breast cancer. Using 22 microsatellite markers located at sites of frequent loss of heterozygosity (LOH) in breast cancer, we analyzed DNA from 16 primary tumors (Stage IIA or more advanced) and 30 longitudinally collected plasma specimens. Clinical data at time of plasma collection was obtained. Every tumor (16/16, 100%) was characterized by an individual pattern of LOH, its tOH fingerprint. LOH in plasma DNA was detected in 12/30(40%) plasma DNA samples, from 8/14(57%) subjects. However, the number of LOH in plasma DNA was small (n=15), and the mean proportional Loli was much lower than in tumors (0.05vs0.52). Although they were infrequent, most LORs in plasma DNA (12/15, 80%) were concordant with abnormalities in the paired tumors, suggesting that they were authentic tumor- derived abnormalities. Despite this, we found no association between plasma DNA LOH and original tumor stage or clinical status at time of blood collection (i. e., LOH was seen as often in subjects who had no evident disease as in those with evident disease). In addition, detection of LOH was not consistent between serial samples from half of subjects (5/11, 45%), despite stable clinical condition. No association with clinical outcome was evident, although the sample size may be too small to be conclusive. Microsatellite instability (MI) in plasma DNA was infrequent, non-concordant with paired tumor, and inconsistent in serial samples. The results of this study suggest that detecting microsatellite abnormalities in plasma DNA of breast cancer subjects may nOt be useful either for detecting occult metastases or for monitoring disease. Other techniques may be more promising but it is possible.