The large numbers of genetic mutations found in cancer cells result in significant challenges for the diagnosis and treatment. The genetic changes are being revealed by large-scale sequencing and microarray measurements of cancer cells. A major difficulty is to determine the mutations that are “drivers” of the cancer from those mutations that have occurred due to faulty DNA repair and transcription in the cancer cells. A number of important genetic mutations are now routinely used in clinical laboratories for the classification of cancer and to determine therapeutic approaches. Reference materials are used to ensure the accurate and reliable results from measurements done in research and clinical laboratories. Established cancer cell lines are very useful to provide renewable reference materials for research and reference materials, but cell lines are selected for their growth in culture and can come with a large number of mutations. A more rational process for developing cell lines is to engineer specific mutations in the cell lines, resulting in a defined genotype. Instead of relying on random transfection methods to introduce mutant genes into the cell, targeted approaches can be used to “knock in” mutant genes to create defined genotypes in the cells. Techniques for producing artificial chromosomes also offer the potential for introducing large amounts of genetic material into cells to study such effects as copy number variations. Gene expression in the engineered cells will be measured using large-scale sequencing, microarrays, and flow cytometry assays. Cell migration and invasion in vitro assays, as well as quantitative live cell imaging are available to measure the effect of the engineered mutations on cell phenotype.

 

Keywords:

Cancer; DNA; Mutations; Sequencing; Cell; Clinical assay; Artificial chromosome; Biomarker;

Citizenship:  Open to U.S. citizens

Level:  Open to Postdoctoral applicants