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Plasma and urinary DNA in patients with breast cancer: potential markers of tumor genetic instability induced by chemotherapy

Grant number: 05/00651-5
Support type:Regular Research Grants
Duration: December 01, 2005 - November 30, 2008
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Auro del Giglio
Grantee:Auro del Giglio
Home Institution: Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil


Patients with various types of solid tumors such as women with breast cancer have higher levels of free DNA in their serum in comparison with normal individuals without tumors (Silva et al., 2002b). Several authors have shown that this DNA present in the serum of these patients is originated from their tumors by experiments in which the same specific alterations - such as the pattern of microsatelite instability present in specific DNA markers - in the serum DNA was also found in their tumors´ DNA (Shao and Nguyen, 2002,Shaw et al., 2000a,Mayall et al., 1999). A recent study conducted by our group showed that chemotherapy regimens, specially those containing alquilating agents, can induce microsatelite instability in the peripheral mononuclear fraction of the peripheral blood of patients with breast cancer in parallel to the decrease of the expression of the DNA repair gene hMSH2 by immunohistochemistry (Fernando LA Fonseca, 2005c). We entertained then the possibility that this finding might contribute to the genetic instability in normal blood cells that could be related to the future development of Mielodysplasia and/or Acute Leukemias, which can happen in about 1% of the breast cancer patients who received alquilating based adjuvant chemotherapy regimens (Casorelli et al., 2003). We thought as well that these microsatelite instability may also happen also in the tumor DNA and if so they could potentially contribute for the tumor to became resistant to chemotherapy... (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PINTO, JORGE L. F.; FONSECA, FERNANDO L. A.; MARSICANO, SARAH R.; DELGADO, PAMELA O.; SANT'ANNA, ALEKSANDRA V. L.; COELHO, PATRICIA G.; MAEDA, PATRICA; DEL GIGLIO, AURO. Systemic chemotherapy-induced microsatellite instability in the mononuclear cell fraction of women with breast cancer can be reproduced in vitro and abrogated by amifostine. Journal of Pharmacy and Pharmacology, v. 62, n. 7, p. 931-934, JUL 2010. Web of Science Citations: 6.

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