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With new method, CSHL team is able to infer how tumors evolve and spread
Date:3/13/2011

ided into many distinct subtypes. Unique markers have been found in a number of cancer subtypes, such as abnormally high levels of the receptor protein encoded by the HER2neu gene, which in a subset of breast cancer cases is a causal factor in oncogenesis. The HER2neu receptor is the target for the pathbreaking drug Herceptin (Genentech Roche).

In the CSHL team's just-published study, the two sampled tumors were known in advance because of prior study -- to represent distinct types. Both were primary invasive breast cancer tumors of the so-called "triple-negative" type, generally regarded as the most aggressive form of breast cancer. One tumor sample was known from prior testing to be polygenomic: composed of distinct populations of tumor cells, whose number, genomic type and evolutionary history were not readily measurable using conventional techniques. The other sampled tumor was monogenomic: composed of cells of a single genetic type. Unlike the first sample, this one had metastasized, to the liver, and samples of that tumor were also subjected to analysis.

Using SNS, in concert with whole-genome amplification and next-generation sequencing, the CHSL team was able to show that in fact three distinct subpopulations of tumor cells were present. "By SNS we could now see that each of these subpopulations was composed of cells that shared highly similar copy number profiles," says Navin. "We could infer that these most probably represent three distinct clonal expansions of the tumor."

Distinct clonal populations as evolutionary 'winners'

Cancer has long been understood to be a clonal disease at the cellular level, with what in evolutionary terms might be called "successful" tumor cells providing the genetic template for the next generation of tumor-cell offspring. The cancer cells comprising the rapidly expanding malignant clone, it is thought, are those best able to survive in the hostile environment of the growing
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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