Large scale genomic instability
Background information - so that you understad more of our focus....
CANCER CAN BE VIEWED AS A GENETIC DISEASE
Tumour cells dont usually start out bad. They generally acquire their malignant properties over years or decades, going from benign to invasive to metastatic to lethal, in a process known as tumour progression (Nowell, P.C., Science 194, 23-28, 1976). This process occurs through a series of mutations and chromosomal aberrations that result in the accumulation of aggressive characteristics by the tumour cells (Hanan, D. & Weinberg, R.A., Cell 100,57-70, 2000). Cancer may therefore be viewed as a genetic disease in the sense that genetic (mutations) and epigenetic (organisational, methylations etc.) changes in cells are probable causes of both initiation and progression of cancer.
Findings of single event changes are extremely rare in cancer. In almost all studies, a multitude of genetic changes are observed.
CANCER CAN BE VIEWED AS A GENETIC DISEASE
Tumour cells dont usually start out bad. They generally acquire their malignant properties over years or decades, going from benign to invasive to metastatic to lethal, in a process known as tumour progression (Nowell, P.C., Science 194, 23-28, 1976). This process occurs through a series of mutations and chromosomal aberrations that result in the accumulation of aggressive characteristics by the tumour cells (Hanan, D. & Weinberg, R.A., Cell 100,57-70, 2000). Cancer may therefore be viewed as a genetic disease in the sense that genetic (mutations) and epigenetic (organisational, methylations etc.) changes in cells are probable causes of both initiation and progression of cancer.
Findings of single event changes are extremely rare in cancer. In almost all studies, a multitude of genetic changes are observed.
CANCER IS ALSO A DISEASE OF DNA ORGANISATION
The organisation of DNA in its cell nucleus is an extremely complex 3-dimensional architecture of a number of different structures, from the simple sugar-phosphate chain to the highly condensed mitotic chromosomes. Normal differentiation relies on a stringent transcription control system with a continual process of activation and deactivation of the different genes. It is generally recognised that chromatin structure can regulate DNA function within the cell, and the overwhelming evidence for rearrangements of the genetic material in tumours, combined with the present knowledge of chromatin structure and function, support the view that cancer is a disease also of DNA organisation (Pienta et al., Cancer Res., 49, 2525-2532, 1989). Changes in DNA organisation and chromatin structure might for example have the same effect as mutation in the above mentioned groups of genes, e.g. by inactivation of a tumour suppresser gene through heterochromatinisation or condensation.