Modeling the aneuploidy control of cancer.

BACKGROUND

Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer.

METHODS

We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm.

RESULTS

Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model.

CONCLUSIONS

The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.