DiagnosticsA Yeast Cancer Model For Mapping Cancer Genes
Researchers have devised a scheme for identifying genes in yeast that
could lead to the identification of new cancer genes in humans. The study
is
published online this week in the open-access journal PLoS Biology.
Cancers arise from the accumulation of mutations or genetic alterations
resulting in the uncontrolled proliferation of cells. However, the number
of
mutations accumulated during the evolution of cancerous cells is large,
making it difficult to identify which of the mutations are responsible for
the
cancer phenotypes. Identifying new genes that sustain cancerous growth is
a major challenge in the campaign against cancers.
Aneuploidy, an abnormality in chromosome number and structure, is a
hallmark of many cancer cells. One idea is that aneuploidy may cause
cancer by
changing the dosage or expression of oncogenes (cancer-causing genes).
After decades of research, only a handful of human oncogenes have been
identified, accounting for a tiny fraction of all cancers So methods of
identifying new oncogenes through their association with aneuploidy has
become an accepted strategy in the cancer field.
The Mcm4Chaos3 mutation causes a defect in an enzyme that unwinds DNA
during DNA replication and predisposes mice to mammary tumors. In this
study, a
team led by Bik Tye from Cornell University introduced the equivalent
mutation in yeast. Yeast with this mutation generate chromosomal
abnormalities
and yield faster growing progeny, a situation reminiscent of what happens
in tumors. Using the yeast genetics tools the researchers could show that
improved growth is not linked to aneuploidy, but to point mutations in
just a few genetic loci.
Pathways and genes that regulate proliferation rates are likely to be
conserved in all eukaryotes. So, by identifying mutations that give cells
growth advantage in yeast, the simplest of eukaryotes, will help guide
the search of cancer genes in humans.
Funding:
This work was supported by National Institutes of Health grant
GM072557 awarded to BKT. The funder had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
Competing interests statement:
The authors declare that no competing
interests exist.
Citation:
"Aneuploidy and Improved Growth Are Coincident but Not Causal in a Yeast Cancer Model."
Li XC, Schimenti JC, Tye BK (2009)
PLoS Biol 7(7): e1000161. doi:10.1371/journal.pbio.1000161
PLoS Biology