Lineage-Specific Transcription Factors in Carcinogenesis

Each cancer is the result of an individually unique evolutionary process. Yet, as demonstrated by extensive genetic analyses of human specimens, the genetic endpoints of cancers across different tissues are remarkably specific, with individual cancer driver genes being typically associated with only a limited set of tumor types. Tissue and cellular contexts thus impose strong and genetically predictable evolutionary constraints on carcinogenesis. Lineage-specific transcription factors, central regulators of organismal development, tissue homeostasis, and regeneration, often also support cancer cell fitness in a lineage-specific manner. In this review, we discuss recent results on the interactions between transcriptional lineage factor programs and oncogenic pathways and how such interactions may determine the oncogenic competence of cancer-associated genetic alterations. These developments are starting to shed light on the molecular basis of tissue specificity in carcinogenesis, with relevance for cancer prevention and therapy.