The research, published in the journal Nature, could ultimately lead to new medicines to fight secondary tumours.
The discovery was made in mice but has been confirmed in human tumour samples.
A UK cancer charity said understanding why some lung cancers are more likely to spread is vital for developing better treatments.
The researchers found the genetic change while studying mice that are genetically programmed to develop lung tumours.
They found reduced activity of the gene – NKX2-1 – in samples from human lung tumours, and found this was associated with higher death rates.
Lead author of the paper, Monte Winslow, of the David H Koch Institute for Integrative Cancer Research at MIT, said understanding the role of the gene may help scientists develop new drugs.
“The sad reality is that if you could tell a patient whether their cancer has turned down this gene, you would know they will have a worse outcome, but it wouldn’t change their treatment,” he said.
The gene codes for a protein that switches other genes on and off.
Cancerous cells which have the gene switched off tend to be more aggressive and more likely to break off from the lungs and spread around the body.
Nell Barrie, senior science information officer at Cancer Research UK said: “Lung cancer is a huge problem worldwide, and understanding why some lung cancers are more likely to spread is vital for developing better, more personalised treatments.
“Research like this is helping to unravel the genetic ‘signatures’ of different cancers, and will spark ideas for new ways to tackle the disease.”