Dissecting genetic heterogeneity within breast tumours
Background
The properties that develop in many breast cancers (metastasis to other organs, resistance to drugs) may be due to cancer stem cells or other rare cells within the tumour. Hormone or chemotherapy may successfully kill the majority of tumour cells, but leave these rare cells intact to initiate new tumours within the breast or at other sites around the body.
At present we do not know how complex the mixture of different cell types within a single tumour may be.
Aims and Relevance
To approach this question we shall make use of a known property of breast cancer cells: a genomic instability that leads to a progressive scrambling of the chromosomes (genome) through breakage and re-joining as cells divide. These mutations are what give tumour cells new functional properties, such as drug resistance.
We will use the presence or absence of specific scrambling events as a sort of genetic fingerprint to determine:
- what cell types are present within advanced breast cancers
- the frequency of each cell type
- the relationship between the different cell types
We expect that these studies will validate our method as a way of distinguishing different cell types within tumours. This is the first step towards identifying the cells that must be destroyed in order to prevent the recurrence or spread of the disease.