Map of cancers reveals how tumours evolve

We now have some of the most detailed maps ever produced of several cancers, as well as new tools and methods for analyzing them. The findings come from an initiative called Cancer Mapping Human Tumor Atlas Networkand provide clues about how cancers form, evolve and become resistant to treatments.

Cancer occurs when genetic mutations stimulate cells to grow and multiply uncontrollably. Much of what we know about the disease comes from genetic analysis of tumors. Until recently, we could only do this by combining and analyzing all the genetic data in a tumor sample at once, making it impossible to identify individual cell types.

But tumors are not singular. “They are complex, like ecosystems, containing not only tumor cells but also immune cells, endothelial cells and other support cells,” said Daniel Abravanel at the Dana-Farber Cancer Institute in Boston.

Thanks to the emergence of more sophisticated tools, a team of researchers has now been able to identify individual cells or determine their function in tumors from nearly 2,000 patients with 20 different cancers.

As part of the job, Li Ding Washington University in St. Louis, Missouri, and colleagues Map 131 tumor areas from 78 patients with cancer types that occur in the breast, colon, pancreas, kidney, uterus, and bile ducts that connect the liver and gallbladder to the small intestine. They used a technique called single-cell sequencing to measure which genes were turned on or off in each cell of the tumor sample.

The researchers also looked at tissue samples under high-power microscopes to determine the location and structure of cells. Next, they built a 3D model of the tumor, showing how cells within the tumor were organized and interacted with each other. They found that within tumors, cancer cells form distinct clusters called microdomains. The researchers then grouped these regions based on similar genetic changes, such as high or low immune cell activity. The evolution of cellular genetic activity in microdomains appears to be a major factor in cancer resistance to therapy.

Further study of the Human Tumor Atlas Network revealed Multiple cells can sometimes coordinate Colon cancer develops. “For decades, the consensus in the field has been that tumors originate from a single cell,” said Doug Winton at Cambridge University.

Winton and his colleagues used mice genetically engineered so that their cells change color when they become cancerous. This makes it possible to identify and track tumors that develop in the intestines of animals. Researchers found that about 40 percent of colon tumors originate from multiple cells that work together to outcompete neighboring cells.

A separate research team consists of Liu Jian Vanderbilt University in Tennessee also Defined biomarkers For monitoring tumor evolution. Naturally occurring mutations produce permanent genetic changes in tissues, allowing researchers to reconstruct the sequence of events to create a molecular timeline of each tumor’s growth.

They used this method to analyze early precursors of colon cancer in mice and humans and found that up to 30% of colon cancers have a multicellular origin. Currently, the best predictor of whether a precancerous colon lesion will become cancerous is its size, Lau said. Understanding how colon cancer develops could improve our ability to screen for precancerous lesions and detect cancer early, he said.

The Cancer Mapping Project uncovered some surprises. Abravanel and colleagues collected 67 tumor biopsy samples from 60 people with cancer. metastatic breast cancermeaning it has spread to other organs, such as the liver, brain, and lungs. They found that samples collected from the same participants at different time points were genetically very similar. “You would expect to see different mutations evolve over time,” Abravanel said.

As part of the project, researchers led Ben Raphael at Princeton University created an algorithm It can quantify the ratio of cancer cells to non-cancerous cells in a tumor and study how these cells interact, which can also help discern how the tumor is growing.

Together, these findings bring us closer to understanding how cancer forms and evolves, allowing for improved treatments. Abravanel says this also helps in his clinical practice: “We do our best to provide the right treatment to the right patient, but to a large extent we are unable to identify the best treatment for individual cases. “It was at that moment. “