Tumour cells may not evolve gradually, but rather in "punctuated or staccato-like bursts", suggests a research letter published in Nature.

The US investigators demonstrated that it is possible to obtain high resolution copy number profiles by sequencing single cells, and that then by examining multiple cells from the same cancer it is possible to make inferences about how the cancer has evolved and spread.

In the study Michael Wigler and colleagues, from Cold Spring Harbor Laboratory (New York, USA), applied a new technique called single nucleus sequencing (SNS) that enables accurate quantification of genomic copy number within a single cell nucleus, indicating the amount of DNA in the nucleus and whether the genome has been amplified or deleted.

The investigators examined tumour population structure and evolution in cells taken from two women with primary invasive breast cancer tumours of the "triple-negative" type. One tumour sample was known from prior testing to be polygenomic - composed of distinct populations of tumour cells; while the other sample was monogenomic composed of cells of a single genetic type that had metastasized to the liver.

Using SNS together with whole-genome amplification and next-generation sequencing, the investigators found three distinct subpopulations of tumour cells to be present. The findings suggest that instead of heterogenous tumour cell populations evolving via gradual evolution, evolution occurs in "punctuated or staccato-like bursts". The authors were also able to show differences in the profiles that distinguished primary and metastatic tumour cells.

"We want to learn how a metastasis grows and we now have the ability to do that at a very detailed level. In a typical blood draw taken from a cancer patient, you will typically see between five and 20 circulating tumour cells, a mark of metastasis. We'll be able to look at every one of them and see if, for example, there's a new clone that is different from the cell populations in the primary tumour," said one of the investigators James Hicks, adding that by looking cell by cell they hope to be able to understand how metastases get built.


Article: N Navin, J Kendall, J Troge, et al. Tumour evolution inferred by single-cell sequencing. Nature. Doi: 10.1038/nature09807.