Related Experiment Video
Updated: May 11, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers
Sophie Rousseaux1, Alexandra Debernardi, Baptiste Jacquiau
1INSERM, U823, Université Joseph Fourier, Grenoble 1, Institut Albert Bonniot, Grenoble F-38700, France. sophie.rousseaux@ujf-grenoble.fr
Abstract:
Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale "off-context" gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature-guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors.
Insights
Cancer cells exhibit abnormal gene activation, leading to a loss of cell identity. This study identifies a gene expression signature in aggressive lung tumors, aiding in stratification and understanding aggressive cancer biology.
Area of Science:
- Epigenetics
- Cancer Biology
- Genomics
Background:
- Malignant epigenetic reprogramming can activate silent, tissue-specific genes, causing cellular identity crises.
- The consequences of this reprogramming, particularly ectopic gene activation, remain largely unexplored in cancer.
Purpose of the Study:
- To investigate the consequences of malignant epigenetic reprogramming by identifying and detecting the expression of epigenetically silenced tissue-restricted genes in cancer.
- To characterize the molecular features of aggressive tumors exhibiting ectopic gene expression.
Main Methods:
- Developed a strategy to identify tissue-restricted genes silenced in normal cells and detect their expression in cancer.
- Analyzed gene expression in 293 lung tumors to identify ectopic gene expression signatures.
- Correlated gene expression profiles with tumor aggressiveness and prognosis.
Main Results:
- Demonstrated large-scale, "off-context" gene activations occur systematically across various cancer types.
- Identified an ectopic gene expression signature in a subset of aggressive lung tumors, predicting poor prognosis.
- These aggressive tumors displayed embryonic stem cell/germ cell gene expression profiles and down-regulated immune response genes.
Conclusions:
- Ectopic gene activation is a common feature in cancer, particularly in aggressive subtypes.
- This finding enables gene signature-guided tumor stratification and the discovery of oncogenic mechanisms.
- Understanding ectopic gene activation expands knowledge of aggressive tumor biology.
