Research ArticleLUNG CANCER

Ectopic Activation of Germline and Placental Genes Identifies Aggressive Metastasis-Prone Lung Cancers

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Science Translational Medicine  22 May 2013:
Vol. 5, Issue 186, pp. 186ra66
DOI: 10.1126/scitranslmed.3005723

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In the Wrong Place and at the Wrong Time

As an old saying goes, there is a time and a place for everything, including gene expression. Unfortunately, cancer cells are not bound by such conventional wisdom. Now, Rousseaux and co-authors show just how problematic lung cancers can be when they turn on the expression of genes that are normally reserved for the placenta and testes.

The authors systematically characterized gene expression in 1776 human tumors from 14 different types of cancer, comparing them to normal samples from a variety of organs. They demonstrated that a subset of genes, called testis-specific/placenta-specific (TS/PS) genes, which are normally active only in the testes or placenta, respectively, was not expressed in any other normal organs. In most of the tumors, however, the TS/PS genes were actively expressed. The authors linked this observation to demethylation of the promoters for TS/PS genes in cancer cells. In a separate series of 293 lung cancer patients at all stages of disease, the authors identified 26 TS/PS genes and showed that expression of these genes strongly correlated with worse prognosis independent of cancer stage.

Future work may replicate these prognostic findings in additional cancer types because experiments from the current study showed evidence of TS/PS gene expression in a variety of different tumors. Additional studies will be needed to validate the TS/PS gene signature in lung cancer and clarify its implications for patient treatment. Someday, with more sophisticated targeted therapies, we may yet be able to teach cancer cells that the adult lung is not the proper time and place for expression of TS/PS genes.