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The normal human esophagus is made up of cells that contain mutations, called mutant clones
.
This new study from the Wellcome Sanger Institute and collaborators at the University of Cambridge uses the most advanced 3D imaging technology and mouse models to visualize tumors under the microscope.
This paper published today (October 13, 2021) in the journal Nature shows that these high mutational cloning burdens create a highly competitive environment in which early tumors under the microscope are The mutant cells are difficult to grow until they are cleared of the tissue
.
Nevertheless, there are still some early tumors that survive and may develop into esophageal cancer
Understanding the mechanisms that prevent most newly formed microscopic tumors from becoming cancer will provide new insights into preventing this disease
.
In a person's life, all tissues of the human body are accumulating mutations
.
In the esophagus, there is a high density of mutant clones that compete for space in order to survive in the tissues
Although most mutant clones contain mutations related to the development of cancer, the rate of tumor formation is not as common as expected*, indicating that there are other factors that prevent the growth of cancer
.
In this study, the team at the Wellcome Sanger Institute, University of Cambridge and other collaborators were able to show that early tumors--up to about 100 cells are difficult to grow in a competitive environment, creating highly competitive mutant clones that carry more mutations.
Favorable mutation
.
This study shows that the survival of early tumors in mice depends not only on the mutations they carry, but also on mutations in nearby normal tissues
.
In addition, it also shows that although some mutations may be the cause of cancer, other mutant clones may have the effect of suppressing tumors, which has nothing to do with the body's immune system
In order to further understand the development of esophageal cancer, it is necessary to further study whether the same interaction exists in human tissues, which mutations cause cancer cells to succeed in this aggressive environment, and the mechanisms behind this
.
Dr.
Korom Bartomeu, first author and senior staff scientist at the Wellcome Foundation Sanger Institute said: “Learning about the highly competitive environment of the esophagus and how cells survive and develop gives us new interactive insights into how surrounding cells affect small cells.
The ability of mice to develop early tumors
.
If we fully understand these interactions, it is possible to find new ways to prevent early tumors from developing into cancer
The author, Dr.
Albert Herms, a postdoctoral fellow at the Wellcome Sanger Institute, said: “From the initial accumulation of mutations to the development of cancer, there are many obstacles that cancer cells need to overcome in adult tissues
.
In this study, we discovered the esophagus.
Dr.
Phil Jones, senior author and senior team leader of the MRC Cancer Unit at the Wellcome Foundation Sanger Institute of Cambridge University, said: "Before our research, it was not understood that the cells of the esophagus may contain many cancer-driving mutations and There are no high tumors
.
Our research reveals part of this puzzle at single-cell resolution.
Journal Reference :
B.
