Children diagnosed with diffuse midline gliomas often die within a year of their initial diagnosis because there is not yet an effective treatment for this rare cancer. But researchers now have a better understanding of what these tumors look like and can work to develop new therapeutic approaches.
A team led by Mariella Filbin, MD, Ph.D., a physician at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, used spatial single-cell transcriptomics to visualize the structure of tumor cancer cells in different age groups and Locations.
The researchers found that the spatial organization of cells could help explain why diffuse midline gliomas are so difficult to treat. The study, published in Natural genetics on December 5, 2022, is the first to use spatially resolved single-cell technology on patient tissue and highlights the need for future therapies to be specialized based on tumor context.
The team focused their study on diffuse midline gliomas induced by a particular genetic change called the Histone3-K27M mutation that causes early brain stem cells to become cancerous.
Dr. Filbin and his colleagues looked for age- and location-related differences in tumors by measuring all gene activity in tissue samples from 50 people, ages 2 to 68, with the Histone3 mutation. -K27M.
The team found that pediatric tumors and brainstem and spinal cord tumors have more immature cells. Immature cells can proliferate quickly and easily due to their similarity to stem cells, which could help explain the lethality of diffuse midline gliomas in children.
The researchers also noticed that adult tumors have more mesenchymal-like cells, which are generally helpful in healing damaged tissue, but may help promote tumor growth and cancer progression. However, the researchers did not detect any underlying genetic cause for this difference.
“Adult tumors seem to be shaped more by the immune microenvironment,” says Dr. Filbin. These results suggest that children and adults with diffuse midline gliomas may need different treatments.
Additionally, the researchers mapped where the gene activity was in space to understand tumor structure and development. What they found was surprising: the cancer stem cells had formed “niches” by clumping together and surrounding themselves with a type of cell that can shield and protect the tumor.
“We now have insight into how tumors organize themselves visually, isolating themselves from the rest of the brain to prevent an immune attack and moving closer to the cells that feed them,” says Dr Filbin. Understanding the structure of the tumor allows researchers to think about new therapeutic approaches.
Dr. Filbin now wants to understand how different cancer cells talk to each other and form a barrier around the tumor so that her team can develop targeted treatments. “If we know how cells communicate, we might be able to block their signaling and prevent them from creating these niches,” she says.
Ilon Liu et al, The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma by age and location, Natural genetics (2022). DOI: 10.1038/s41588-022-01236-3
Provided by Boston Children’s Hospital
Quote: Using Spatial Single Cell Transcriptomics to Visualize Diffuse Midline Glioma (2022, Dec 5) Retrieved Dec 6, 2022 from https://medicalxpress.com/news/2022-12-spatial-single-cell-transcriptomics-visualize-diffuse .html
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