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UCSF Researchers Use New Tools to Move in on Cancer Susceptibility Genes
Date:1/12/2009

d mice.

"Now we have shown Vdr can be linked to skin cancer in mice using genetic network analysis methods," says Balmain. Because man and mouse share significant similarities in cancer genetics and cancer development, he says, gene candidates for cancer in mice could directly translate into gene candidates for cancer susceptibility in humans.

Genetic networks comprise dozens or hundreds of genes that interact by switching on and off in response to internal stimuli, external stimuli, or some combination of both.

This switching process, called gene expression, has been extremely difficult to measure and assess due to the sheer numerical complexity of the process. In part, this complexity explains why most cancer genetics research to date has focused on identifying clear interactions between single genes and a specific type of cancer. However, these approaches so far have not been sufficient to explain how gene expression impacts susceptibility to many types of cancers.

The researchers also used their technique to identify gene networks that appeared to represent either structural or functional components of the skin, such as skin-resident cell types (hair follicles, muscle, melanocytes, haematopoietic cells) and physiological (for example, inflammation) or cellular (for example, cell cycle) functions.

They discovered that a gene called Lgr5 that is expressed in stem cells of the skin and intestine is a candidate master regulator for the development of hair follicles. In the context of skin cancer, hair follicle development may be important because the hair follicle is a continuously regenerating organ system. Scientists have used this system as a model for studying cancer development in different organs.

According to the researchers, their research approach could easily be replicated for genetic network analysis of virtually any type of moderately or partially heritable cancer, as well as for other
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