Researchers at the University of Hawaii Cancer Center have discovered that mesothelioma is the result of mutations in more than one cell. This seemingly minor discovery could open up new possibilities in the future for research and more effective treatment.
Mesothelioma was previously believed to be the result of a mutation in a single cell, and research led by Dr. Michele Carbone recently turned this assumption on its head.
The article, “Evaluation of clonal origin of malignant mesothelioma,” was published in the Journal of Translational Medicine.
Using Cell Biology to Further the Understanding of Mesothelioma
All cancers are the result of mutations occurring in healthy cells; in the case of mesothelioma, asbestos causes abnormalities in healthy cells that make up the lining of the lungs, chest, heart and abdomen.
Mesothelioma was previously believed to be a monoclonal cancer—a cancer that starts with the mutation of a single cell. When cells in the body divide, every so often an abnormal cell appears. Usually these cells are destroyed by the immune system. But when a mutated cell survives, it can start replicating uncontrollably and form a tumor. A tumor in this scenario is a monoclonal cancer because the cells making up the tumor are descendants of a single cell.
This is how scientists originally understood mesothelioma to develop. At one time, biologists even suspected all types of malignant tumors to be monoclonal. Yet, Dr. Carbone’s research has shown that mesothelioma is a polyclonal cancer—a cancer caused by a simultaneous mutation in many individual cells.
“Our study indicates that malignant mesothelioma is the result of polyclonal tumors, a finding that has implications for our understanding of the disease and the clinic,” Dr. Carbone said.
Chromosomes and Clonality
The researchers in this study used HUMARA (Human Androgen Receptor) assay on 16 tissue biopsies from 14 women with mesothelioma. The assay is essentially a way of comparing genetic material inside the various biopsies.
The gender-specificness of the biopsies was also necessary to understanding the clonality of the samples.
Inactivation of X chromosomes occurs randomly in developing female embryos. The inactivated chromosomes that occur in women can be a way of tracing back the ancestry of cancerous cells to determine their origin. That is, it allows researchers to determine if the cancerous cells all came from a single mutated cell.
The inactivation of these chromosomes inside the female’s cells is the key to determining the clonality of a cancer because all future descendants of this cell have the same inactivated chromosome.
Comparing the inactivated chromosomes inside various cells allowed the researchers to discover that the tissue biopsies in the study had cells with different inactivated chromosomes. They were polyclonal.
The Future of Mesothelioma Research
The latency period of mesothelioma may be behind the reason for its polyclonal nature. It can take up to 50 years after being exposed to asbestos for mesothelioma to develop. During this time, asbestos fibers remain lodged into the lining of the lungs or abdomen, potentially triggering multiple cell mutations throughout this time.
The presence of several molecular starting points for mesothelioma might also help explain why patients often relapse after treatment.
“Patients that have their tumors removed at the early stages of this type of cancer will most often go on to have a recurrence in spite of the appearance of the eradication of malignant mesothelioma,” Dr. Carbone said. “This new insight helps us understand why that may be.”
A more complete understanding of the cellular origins of mesothelioma may allow researchers to develop a treatment that attacks multiple cell clones. Cell clones are a group of cells that came from the same cell. In a polyclonal cancer, there are several different cell clones with different molecular characteristics.
Recognizing that mesothelioma is a polyclonal cancer unleashes a new way of thinking about treatment and research. This understanding could have new implications for novel treatments and eventually extending the lives of mesothelioma patients across the country. The future of mesothelioma research has just reached a new turning point.
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