Ras gain of function mutations are found in 20-30% of all human cancers. When C. elegans have a gain of function mutation in their sole Ras, encoded by a gene called let-60, they inappropriately activate the cell cycle and develop variable numbers of extra cells never found in wild-type animals. Yet, not all of the animals with this mutation succumb to this phenotype.
Interestingly, many people with risk alleles for certain kinds of cancer also never develop cancer. What affects the penetrance of these dominant negative gain of function alleles? The Mendenhall lab is working to identify genetic and environmental factors that influence the penetrance of Ras signaling. For example, they have found an association between increased chaperone reporter expression and increased penetrance and expressivity.
Interestingly, many people with risk alleles for certain kinds of cancer also never develop cancer. What affects the penetrance of these dominant negative gain of function alleles? The Mendenhall lab is working to identify genetic and environmental factors that influence the penetrance of Ras signaling. For example, they have found an association between increased chaperone reporter expression and increased penetrance and expressivity.