Genetic similarities between organogenesis and tumorigenesis of the lung.
In hematological malignancies, there are numerous examples of lymphocyte developmental genes playing a role in cancer formation. In this article, we discuss how processes of fetal organogenesis are also operant in lung tumorigenesis. We first review four pathways important in lung cancer (MYC, Hedgehog, Rb and Wnt) and describe the experimental evidence linking them to lung development. Then, we review genome-wide analysis approaches of both RNA (gene expression profiling) and DNA (copy number alterations) and how they have uncovered links between lung cancer and fetal lung development. Finally, the recent discovery of three closely linked developmental transcription factors, which are co-amplified as cooperating lung oncogenes, is discussed. We suggest that inhibition of the fetal developmental pathways selectively reactivated in cancer cells is a research area of interest for novel anti-cancer therapies in light of the presumed low toxicity of such therapies to the nearby normal adult cells.
Powers
Scott
S
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York USA.
Mu
David
D
D000818:Animals; D006801:Humans; D008168:Lung / Q000196:embryology*; D008175:Lung Neoplasms / Q000235:genetics*; D038081:Organogenesis / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors