The clue of genomic instability in breast cancer

New research has shown, using human tissue biopsies – a hypothesis that until now could only be argued indirectly using cell cultures – that the significant increase in genomic “disorder” that is associated with breast cancer occurs in the transition between the typical hyperplasia and the in situ carcinoma, coinciding with a reduction to a critical minimum in the cell chromosome terminations (known as telomeres). This process of critical reduction, occurring due to the accumulation of cell divisions, causes problems in the cell division process, giving rise to cells with an abnormal genetic content. These cells are normally detected and eliminated from the organism thanks to a complex control and defence mechanism, but the activation of a protein known as telomerase is capable of short-circuiting these defence mechanisms and perpetuate these cells with abnormal genetic content, facilitating the development of the cancer.

The research work was carried out in the prestigious Lawrence Berkeley National Laboratory of the US Department of Energy at Berkeley (California) in collaboration with the University of California in San Francisco.

The contribution of the Spanish scientists Carlos Ortiz de Solórzano and Enrique García Rodríguez to the research was the development of programmes for the analysis of images from confocal 3D microscopy by which each cell can be observed separately and the amount of DNA in each cell nucleus determined. The number of de copies of genes involved in the development of the cancer and the number and length of the telomeres of these cells can be thus determined. This study would not have been possible without the 3D scientific visualisation programmes. The task group at the Lawrence Berkeley National Laboratory was directed by Dr. Carlos Ortiz de Solórzano, who leads a microscopy and biomedical image analysis group.

The work published by the latest number of Nature Genetics, one of the scientific journals with most impact in the field of biomedical research and the magazine of reference for genomic investigation, suggests that persons with benign tumours and who have a greater risk of developing cancer could be identified at an early stage by measuring telomerase activity; it opens the doors to the development of new therapeutic agents that selectively eliminate the tumorous cells, avoiding the reactivation of the telomerase enzyme in cells with an abnormal genetic content, or eliminate cells where the enzyme has been reactivated.

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