Genomic instability en route to and from cancer stem cells.

Cancer is caused by successive gene mutations that amount to confer malignant phenotype. Genomic instability (GIN) is considered a key endogenous mechanism for accumulation of mutations, and therefore, has been proposed as an engine of tumorigenesis. Recently, cancer stem cells, or tumor initiating cells, have been identified in a variety of human cancers. These cancer stem cells (CSCs) are believed to be responsible for the initiation of malignant growth and metastasis of some, and perhaps all cancer types. How are these two engines of tumorigenesis related to each other? Is GIN a driving force in the genesis of cancer stem cells? Is the genome in CSCs inherently unstable? Could GIN in CSCs be the cause of the observed cancer cell heterogeneity? In this article, we will discuss some early clues indicating that these two driving forces of tumorigenesis appear to be intimately connected.