Cancer from asbestos caused by more than one cell mutation

December 8, 2014  |   |  1 Comment
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Asbestos fibers travel through the airways to the lungs and reach the pleura, exposing many mesothelial cells. (credit: Evaluation of clonal origin of malignant mesothelioma in Journal of Translational Medicine)

It has been a long-held belief that tumors arising from exposure to asbestos are caused by mutations in one cell, which then produces multiple clones. This hypothesis is challenged by new research published in the open access Journal of Translational Medicine, which suggests it is caused by mutations in multiple cells.

Malignant mesothelioma is a rare form of cancer that affects the mesothelium – the protective lining that covers the internal organs, such as the lungs, heart and abdominal cavity. It is estimated that malignant mesothelioma affects up to 3,200 people in the U.S. each year, most of whom die within a year of diagnosis. The primary cause of this cancer is exposure to asbestos, which was previously used in building construction. The inhalation of asbestos fibers causes inflammation that can cause mutations in cells even after 30-50 years of dormancy.

Most cancers are thought to be monoclonal, where all the cells in a tumor can be traced back to a mutation in a single cell. Researchers from University of Hawaiʻi Cancer Center set out to investigate whether this was the case with malignant mesothelioma, or if it was polyclonal in which the tumor is the result of the growth of two or more mutant distinct cells.

During early development of the female embryo, one of the two X chromosomes becomes inactivated and this inactivation is passed on to all subsequent cells. By tracing this inactivated X using a process called HUMARA assay, it is possible to determine whether or not a cancer is monoclonal.

In this study, 16 samples from 14 tumor biopsies from women with mesothelioma had a HUMARA assay performed on them. These were compared to control DNA samples from a healthy male and female, and a known monoclonal cell line. The samples provided insight into the origin of the tumors and they were found to be polyclonal.

Implications for future research

Carbone

Michele Carbone

Said lead researcher Michele Carbone from the UH Cancer Center, “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. For example, 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. This new insight helps us understand why that may be.”

These findings have implications for future research, especially with the advent of genomic medicine in the treatment of tumors. These results suggest that future approaches should target polyclonal cancerous cells with different types of mutations rather than a single monoclonal cell.

Added Carbone, “Our findings underscore the need to attack simultaneously several different molecular targets to try to eliminate the different malignant mesothelioma cell clones, as each clone may carry its own distinct set of molecular alterations.”

A UH Cancer Center news release

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  1. TE.Y. Uʻilanimakamaekapolipumehana Kūhaulua says:

    Welina mai kākou! I recently got deathly sick from removing a rug and padding that was over 35 years old. When I scraped the ground to loosen some stuck padding, as I breathed in, My whole upper chest burned intensely. I told everyone this and they dismissed it.
    4 days later, I couldnʻt think straight, I had a fever of 110 degrees Fahrenheit, and couldnt urinate. I also was hallucinating. anyway, went to hospital and long story short, I died. I feel that I was poisoned by asbestos and am afraid of any after affects. My reaspn for not being dead is attributed to prayer, because the hospital gave up on resusitating me and recorded my time of death, and told my husband I was gone. Thatʻs when God stepped in. I had total internal organ failure, My lung was punctured by the dr. and it collapsed around my allready struggling heart and suffocated it to death. No one could find what caused my illness so I was sent to straub in critical condition, icu, 24/7 Dialysis, and in a coma for 3 weeks. When I died I was with out oxygen for 16 minutes. However God spared my brain. I have a lot of things wrong with me but Iʻm here. My question? How can I find out now in 2014. That happened in 2011.

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