Abstract C16: Expression of the serum CAN SINEs sequences as a prognostic marker in canine mammary cancer.

Abstract

Abstract Breast cancer is a global concern and it is the most common cancer that affects women and the fifth leading cause of death cancer related. The study of canine mammary tumors is an excellent model for clinical and pathologic investigation, helping the better understanding of diagnosis and prognosis of breast cancer. The genome of mammals is characterized by a large number of repeated sequences, remnants of transposable elements and the SINEs sequences (short retrotransposons) are characteristics of the canine species. Studies have shown that small amounts of DNA freely circulate in normal blood serum and high amounts are found in patients with cancer, characterizing it as a candidate tumor-biomarker. The aim of this study was to quantify the CAN SINE element by estimating the number of copies in bitches with mammary cancer and to assess its relationship with the clinical course and survival in order to predict its probable prognostic value. The sequence of the CAN SINE element of 174pb was cloned, quantified and was set the initial value of plasmid copies. It was estimated the number of copies by PCR in real time in 28 bitches with mammary neoplasia. By univariate analysis, it was observed an increase in the number of copies in female dogs that had died when compared with dogs that had survived (p=0.02). For the survival curve analysis, it was established a cutoff value of 19.132.000 copies, making possible the correlation between the increase of the number of copies and the low rate of survival of the group (confidence interval - 95%, p=0.04). The increase and/or genetic and epigenetic changes in serum DNA have been associated with worst prognosis in several tumors and there are reports that, around 50% of all cancer patients have increased of free circulating DNA. In healthy people, the process of apoptosis is the main source of free circulating DNA, in contrast, the DNA released from malignant cells varies in size, because the pathological cell death in malignant tumors results not only from apoptosis but also from necrosis, autophagy and/or mitotic catastrophe. Thus, high levels of CAN SINEs fragments can be great markers for the detection of tumor DNA in blood. All bitches that had died showed increased in copy number, implying a higher release of free circulating DNA associated with malignant cellular changes that occur in cancer and this estimate indicates the independent prognostic for survival and can be used in stage control of mammary cancer. The increase in the number of copies of the CAN SINE element observed in this study may characterize it as a marker of poor prognosis, being related to bitches with shorter survival. This estimation can be used as a prognostic marker in non-invasive breast cancer research and is useful in predicting progression and patient monitoring. A quick and minimally invasive test to the patient as the index of DNA in blood, this tumor marker is a powerful predictor of the prognosis of cancer and in addition, can be an innovative and accurate marker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C16.