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Tumor DNA in plasma of breast cancer patients. Relation to treatment

ADN tumoral en plasma de pacientes con cancer de mama. Relación con el tratamiento

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Abstract

Background

The present study was designed to investigate the possible impact of treatment on changes in plasma DNA showing tumor DNA features in breast cancer patients.

Methods

Thirty-eight patients were included. DNA extracted from tumor and normal tissues, normal blood cells, and plasma was used for molecular studies. Molecular alterations in six polymorphic markers (TH2, D10S197, D16S421, D17S855, D17S654, D9S161), mutations in TP53, and aberrant methylation of the first exon of p16INK4a were used to characterize tumor and plasma DNA. After mastectomy, 26 patients received adjuvant chemotherapy and 12, hormone therapy.

Results

At least one molecular alteration was detected in 28 tumors, and 9 patients showed more than one concomitant molecular change. Twenty patients (53%) displayed loss of heterozygosity (LOH), 6 (16%) TP53 mutations and 11 (29%) methylation of the first exon of p16INK4a. The same molecular aberration was observed in plasma DNA of 18 patients (14 receiving chemotherapy and 4 hormone therapy). Six months after mastectomy, these molecular alterations persisted in the plasma DNA of 6 patients (5 who had completed adjuvant chemotherapy and 1 under hormone therapy).

Conclusions

Circulating plasma DNA present after mastectomy is modified only partially by adjuvant chemotherapy or hormone therapy.

Resumen

Fundamento

Este trabajo fue diseñado para estudiar el posible impacto adyuvante sobre las variaciones de ADN libre en plasma con características del ADN tumoral en pacientes con cáncer de marna.

Métodos

Se estudiaron 38 enfermas. El ADN para el análisis molecular fue extraído de tumor y del correspondiente tejido normal, de linfocitos y del plasma. Se utilizaron como marcadores para caracterizar el ADN 6 microsatélites (TH2, D10S197, D16S421, D17S855, D17S654 y D9S161), las mutaciones en TP53 y metilación aberrante del primer exón de pl6INK4a. Después de la mastectomía, 26 pacientes recibieron quimioterapia adyuvante y 12, hormonoterapia.

Resultados

Se detectó al menos una alteración molecular en 28 tumores, y en 9 casos un mismo tumor presentó más de una alteración molecular simultáneamente. Veinte tumores (53%) presentaron pérdidas de heterocigosidad (LOH), 6 tumores (16%) mutaciones en TP53 y 11 tumores (29%), metilación aberrante de p16INK4a. La misma alteración molecular se observó en el ADN plasmático de 18 pacientes, 14 de las cuales recibieron quimioterapia y cuatro, hormonoterapia. Seis meses después de la mastectomía, 6 pacientes mantenían las mismas alteraciones moleculares en el ADN plasmático, cinco correspondientes al grupo de quimioterapia y una al de hormonoterapia.

Conclusiones

El ADN libre en plasma, similar al ADN tumoral, puede encontrarse después de la mastectomía y el tratamiento adyuvante sólo modifica parcialmente este parámetro.

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Authors and Affiliations

  1. Medical Oncology Service, Molecular Genetics Unit. Clínica Puerta de Hierro, Madrid

    José M. Silva, Antonio Sánchez, Celia Miralles, Fátima Navarro & Félix Bonilla

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  1. José M. Silva
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  2. Antonio Sánchez
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Silva, J.M., Sánchez, A., Miralles, C. et al. Tumor DNA in plasma of breast cancer patients. Relation to treatment. Rev Oncología 2, 141–145 (2000). https://doi.org/10.1007/BF02979481

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  • DOI: https://doi.org/10.1007/BF02979481

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