Cancer from asbestos caused by more than one cell mutation

December 3, 2014, BioMed Central

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 that affects the mesothelium - the protective lining that covers the internal organs, such as the lungs, the heart and the abdominal cavity. It is estimated that affects up to 3,200 people in the USA each year, most of whom die within a year of diagnosis. The primary cause of this cancer is exposure to asbestos, which used to be used in building construction. The inhalation of 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 Hawaii 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.

Lead researcher, Michele Carbone from University of Hawaii, says: "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.

Michele Carbone says: "Our findings underscore the need to attack simultaneously several different molecular targets to try to eliminate the different malignant cell clones, as each clone may carry its own distinct set of molecular alterations."

Explore further: Researchers find potential new target to treat malignant pleural mesothelioma

More information: Evaluation of Clonal Origin of Malignant Mesothelioma , Sabahattin Comertpay, Sandra Pastorino, Mika Tanji, Rosanna Mezzapelle, Oriana Strianese, Andrea Napolitano, Francine Baumann, Tracey Weigel, Joseph Friedberd, Paul Sugarbaker, Thomas Kruasz, Ena Wang, Amy Powers, Giovanni Gaudino, Shreya Kanodia, Harvey Pass, Barbara Parsons, Haining Yang and Michele Carbone , Journal of Translational Medicine 2014, 12:301 www.translational-medicine.com/content/12/1/301

Related Stories

Researchers find potential new target to treat malignant pleural mesothelioma

July 25, 2013
Malignant mesothelioma is a rare asbestos-associated malignancy with limited therapeutic options. Despite advances in the treatment, the median survival remains 12 months from the time of diagnosis. Increased understanding ...

Genetically modified cells learn to fight mesothelioma

November 6, 2014
It's been called the "fifth pillar" of cancer treatment: genetically re-engineering the human immune system to recognize cancers and fight them.

Curcumin, special peptides boost cancer-blocking PIAS3 to neutralize STAT3 in mesothelioma

September 18, 2014
A common Asian spice and cancer-hampering molecules show promise in slowing the progression of mesothelioma, a cancer of the lung's lining often linked to asbestos. Scientists from Case Western Reserve University and the ...

Cancer researchers discover gene defect responsible for cancer syndrome

September 6, 2012
University of Hawai'i Cancer Center researchers have discovered germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and atypical ...

Renal cancer drug temsirolimus shows promise against mesothelioma

May 1, 2011
A drug commonly used to treat kidney cancer may increase the effectiveness of chemotherapy for mesothelioma, according to a study published in the May issue of the Journal of Thoracic Oncology.

Mesothelioma risk endures over long-term

September 22, 2014
Western Australian researchers have determined the risk of developing mesothelioma continues to increase even 40 years after a person's first exposure to asbestos.

Recommended for you

Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018
Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature ...

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.