Novel Approach Gives Insights Into Tumor Development

NIH | MARCH 24, 2015

Lung cancer is the most common cause of cancer deaths. Past studies have found many genetic alterations involved in lung cancer development. However, tumor growth and metastasis occurs amid complex, evolving, and diverse genetic changes.

To systematically test the effects of mutations across the cancer genome, researchers at the Massachusetts Institute of Technology and their colleagues used a technique called a CRISPR-Cas screen to disrupt specific sequences.

Bacteria use the CRISPR-Cas system to protect themselves from invaders. Short stretches of genetic material from bacteriophages (viruses that attack bacteria) and plasmids (pieces of DNA exchanged between bacteria) are incorporated into the system to detect targets for destruction in the future.

When injected under the skin of immunocompromised mice, the collection of mutant cells formed tumors at the injection site that metastasized to the lungs. Cells with greater ability to proliferate dominated the tumors over time, and that metastases were seeded by a small set of cells.

Mutations in many of the identified genes have been implicated in human cancers. When the team analyzed gene expression in metastatic tumors from patients with non-small-cell lung cancer, most of the genes (up to 75%) were downregulated.

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