Cancer stem cell genomics: the quest for early markers of malignant progression.

Biologically distinct populations of neoplastic stem cells have been identified in a variety of human cancers, in which they are associated with the initial steps of tumorigenesis. The intrinsic properties of self-renewal, clonogenicity and multipotency, along with a longer half-life within the body, may render normal adult stem cells more prone to accumulate genetic mutations leading to neoplastic transformation, as predicted by the cancer stem cell hypothesis. Tumor formation is also associated with the pluripotency of embryonic stem cells and may be induced as a consequence of complete dedifferentiation of mature cells, as recently reported for induced pluripotent stem cells. The tumor-initiating cell phenotype may result from genetic alterations affecting the expression of critical genes regulating typical stem cell processes such as self-renewal and pluripotency, in addition to genes determining stem cell senescence or longevity. Detailed genome-wide analysis of cancer stem cells and respective normal counterparts will help elucidate the cellular and molecular nature of tumors, providing fundamental information about the initial steps toward malignant transformation. Devising ways of detecting such genetic and epigenetic alterations and cell populations displaying them would allow medical interventions at the early phases of cancer development, thereby improving the chances of favorable clinical outcomes.