Genetic mutation related to thyroid hormones may play part in mesotheliomaThe cutting edge of mesothelioma research is genetic sequencing. This method analyzes the effect that asbestos exposure has on DNA - namely, it can help scientists understand which points in the human genome are most vulnerable to fiber-induced mutations and which are most likely to lead to pleural disease.
For example, a new study out of the University of California, San Francisco (UCSF) has revealed that a gene associated with thyroid hormone receptors may, if damaged by asbestos, play a role in the development of respiratory malignancy.
It's all in the proteins
The investigation itself took place in UCSF's Thoracic Oncology Laboratory and its Comprehensive Cancer Center, thanks in part to funding provided by the Kazan, McClain, Abrams, Fernandez, Lyons, Greenwood, Harley and Oberman Foundation.
Using sophisticated gene sequencing techniques, the researchers found an unusual (but telling) mutation in the DNA of a man with extensive thoracic malignancies. The patient's genes had been damaged in a region that controls TSHR, or the thyroid-stimulating hormone receptor.
What do thyroid hormones have to do with mesothelioma and other respiratory cancers? Directly, not much - but indirectly, this receptor is tightly linked to pleural disease.
That's because the TSHRs on respiratory cells can bind with NK2 homeobox 1 (NKX2-1), also known as thyroid transcription factor 1. NKX2-1 is a protein that helps control the transcription of the DNA and maintains thyroid and lung cell growth.
When people are diagnosed with respiratory malignancies, they often have high levels of NKX2-1 in their blood, according to landmark studies published in the journals Nature and Oncogene.
TSHR may be a good target for early detection methods
So, while NKX2-1 helps doctors diagnose diseases like mesothelioma once they occur, tests for TSHR overexpression might help oncologists pinpoint the risk of respiratory cancers early, before such illnesses become full-blown.
However, the team noted that TSHR mutations, while clinically significant, aren't too common.
"Our observed mutation frequency of TSHR is ~1 percent (1/96) in lung adenocarcinoma patients, which suggests that mutation of TSHR is not a major event in lung carcinogenesis generally," the group explained. However, "when considering a significant overexpression of TSHR in tumor compared to matched normal samples, TSHR protein, not DNA or mRNA, may be used for either diagnostic or therapeutic purpose."
Such advancements give hope to the thousands of Americans suffering from mesothelioma. Each year, 3,000 adults in the U.S. are diagnosed with the disease, according to the American Cancer Society.
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Protein may serve as a new target for mesothelioma treatment, http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2012519a.html, 11/28/12
Antibodies may help diagnose malignant mesothelioma, http://www.rjme.ro/RJME/resources/files/531312817820.pdf, 11/28/12
Cellular molecule makes mesothelioma cells vulnerable to radiation, http://ar.iiarjournals.org/content/32/11/4871.short, 11/26/12