This 'family tree' tells the story of how a cancerous tumor grew

It's the most comprehensive "family tree" of a tumor ever created.
Grant Currin
A lung MRI, a phylogenetic tree developed by the researchers.1, 2

Reserachers have created the most comprehensive history of a cancerous tumor ever.

They used genetic engineering to give lung cancer to some very unlucky mice. Then they collected cells from the tumors, sequenced the DNA from each one, and rewound the clock to watch how a few malignant cells developed into cancerous tumors capable of spreading throughout the body.

Their “family tree” shines light on a handful of genes that seemed to make some lineages of malignant cells more likely to survive, thrive, and eventually spread.

“Revealing the relationships between cells in a tumor is key to making sense [of how they grow] and gaining insight into the emergence of aggressive states,” says computer scientist Nir Yosef, a co-author on the study. It was described in a paper published Thursday in the peer-reviewed journal

Genetic engineering and computational methods gave the researchers incredible insight into the tumor's development

The researchers created a virus that simultaneously triggered mutations that caused lung cancer and de-activated a gene that suppresses tumor growth. The virus also enabled them to tag each malignant cell with a DNA “barcode” that made it possible to track that cell’s descendants through the generations. Each time one of the barcode-carrying cells divided, the series of A, T, C, and G molecules in a certain section of its genetic code changed very slightly. 

Biologist Tyler Jacks, a co-author, says that, under these circumstances, tumors the lungs of these mice closely resemble the tumors that develop in humans. “In this model, cancer cells develop from normal cells and tumor progression occurs over an extended time in its native environment,” he says. “This closely replicates what occurs in patients.”

The insights could one day lead to treatment in humans

When the researchers harvested the cells and sequenced their DNA, they were able to use the information to construct a family tree of the tumor’s cells. That’s valuable information because tumors evolve — at a genetic level and in the expression of genes — as they grow. The family tree enables researchers to determine when and how the cancer became more aggressive, more resistant to treatment, and more inclined to spread to other parts of the body.

“Previously, the critical events that cause a tumor to become life-threatening have been opaque because they are lost in a tumor’s distant past, but this gives us a window into that history,” says cancer researcher Jonathan Weissman, another co-author.

The family tree gave the researchers an important insight into how tumors metasticize, allowing them to spread and grow more tumors elsewhere in the body. The cells most likely to metasticize had descended from aggressive cells that had managed to grow and survive when the tumor was younger. It was only in the tumor’s later stages that those lineages began to metasticize. It turns out that these cells share some of the same genes. That gives researchers developing cancer treatments concrete targets.

“In the future, we want to be able to look at the state of the cancer cells when a patient comes in, and be able to predict how that cancer’s going to evolve, what the risks are, and what is the best treatment to stop that evolution,” says cancer researcher Dian Yang, another co-author. “In order to develop better therapies, it’s important to understand the fundamental principles that tumors adopt to develop."

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