Even with a sound assay design, cancer biology
is a brutal battleground for putting technologies
to the test. Doctors and clinical researchers have
long recognized tumors as highly heterogeneous
masses of healthy and cancerous cells, with the
latter population in constant flux as new alterations
emerge and are selected for over the course
of progression and treatment.
However, the problem may be even more
extensive than previously expected. In one
notable report from a team led by Charles
Swanton at the Cancer Research UK London
Research Institute3, researchers collected
numerous biopsies from primary tumors and
metastases in four patients with renal cell
carcinoma and uncovered startling diversity.
Their findings support a model in which
tumors are initiated by cells containing ‘trunk’
mutations, which over time mutate to give rise
to diverse ‘branch’ clonal populations. In this
‘branched evolution’ model, different branches
are likely to share the same common trunk
mutations, but accrue a host of other mutations
that might later prove advantageous.
“There was heterogeneity at every level,” says
Swanton. “From DNA copy number to mutations
to gene expression to function; in fact,
heterogeneity seemed to outweigh what was
in common.” His team even found that biomarker
analysis of two different samples from