Telomerase RNA as a detection marker in the serum of breast cancer patients

Tumor-derived circulating DNA has been found in the plasma of cancer patien ts. Alterations include decreased strand stability, mutations of oncogenes or of tumor suppressor genes, microsatellite alterations, and hypermethylat ion of several genes, RNA has also been found circulating in the plasma of normal subjects and cancer patients. Tyrosinase mRNA has been extracted fro m the serum of melanoma patients and subjected to RT-PCR. Moreover, the pre sence of cell-free EBV-associated RNA has been reported in the plasma of pa tients with nasopharyngeal carcinoma. Human telomerase comprises two RNA su bunits, telomerase RNA template (hTR) and its catalytic component, telomera se reverse transcriptase protein (hTERT). Expression of these subunits corr elates with telomerase activity. Using RT-PCR, we investigated whether thes e RNA subunits were present in the serum of 18 patients with breast cancer, 2 patients with benign breast disease, and 21 normal subjects. The presenc e of amplifiable RNA was confirmed in all tissue and serum samples using RT -PCR of glyceraldehyde-3-phosphate dehydrogenase RNA. hTR was found in 17 o f 18 tumors (94%) and 5 of 18 serum samples (28%). hTERT was also detected in 17 of 18 tumors (94%) and in 4 of 16 available serum samples (25%). hTR and hTERT were undetectable in tissues and sera taken from 2 patients with benign disease and in the sera of 21 normal subjects. We conclude that RNA is detectable in the serum of breast cancer patients and that tumor-derived mRNA can be extracted and amplified using RT-PCR, even in patients with lo calized disease. This may have implications for cancer diagnosis and follow -up in the future.