A new study identifies previously unknown genetic alterations behind mesothelioma – a rare and deadly cancer whose main cause is exposure to asbestos. The findings include some mutations that may serve as new targets for treatment and others that could help improve the diagnosis, screening and prediction of outcomes for patients.
In a paper published in Nature Genetics, the team – from Brigham and Women’s Hospital (BWH) in Boston, MA, and Genentech in San Francisco, CA – reports how they carried out a comprehensive genomic analysis of over 200 mesothelioma tumors.
Lead author Dr. Raphael Bueno, chief of BWH’s Division of Thoracic Surgery and co-director of the hospital’s Lung Center, says because they were able to analyze so many samples for such a rare disease, they were able to identify a “spectrum of mutations.”
He says some of the mutations they uncovered have been found in other cancers, and drugs that target them are already developed. He adds:
“No one knew before now that these mutations might also be found in mesothelioma tumors. This new work suggests that patients with such mutations may benefit from certain existing drugs.”
Genomic analysis is a growing field where scientists use cutting-edge DNA sequencing technology and information systems to identify, measure and compare the genetic information and processes that influence cell behavior.
Using such tools, scientists can map the genetic alterations that cause cells to malfunction and give rise to cancer.
Malignant mesothelioma – often shortened to mesothelioma – is a rare but deadly cancer that arises when tumor cells form in the thin layer of tissue that covers the lung, chest wall or abdomen.
- People exposed to asbestos at an early age, for a long time and at higher levels, are at higher risk of developing mesothelioma
- Unfortunately, the risk does not go down over time after the exposure to asbestos stops
- The risk appears to be lifelong – some cases are first diagnosed 50 years after exposure.
The cancer can also develop in the heart or testicles, but this is very rare.
The major cause of mesothelioma is being exposed to asbestos over a period of time. This includes people exposed to asbestos in the workplace and their family members. It usually takes 20 years or more for the cancer to develop.
The 5-year survival for mesothelioma is 5-10%. Every year in the US, over 3,200 people are diagnosed with the cancer, and around the same number die of the disease.
While aggressive surgery can help some patients, current treatments do not help those with advanced disease.
For their study, the team analyzed 216 malignant pleural mesothelioma (MPM) tissue samples and compared normal tissue to cancerous tissue. MPM is the most common type of mesothelioma – it develops in the pleura, the thin layer of tissue surrounding the lungs.
They found over 2,500 alterations in DNA and RNA (the molecules that translate DNA code into instructions for cells to follow) and identified 10 significantly mutated genes. They also captured information about immune cells at the site of the tumor.
The researchers suggest some of the mutations they found could be targeted by therapies that already exist – such as a BCR-ABL-1 inhibitor that targets fused genes – and they could be matched to a patient’s tumor.
Knowledge about some of the other mutations could also help pathologists improve the accuracy of mesothelioma diagnosis and predict which patients will have poor or better outcomes.
In another example, the researchers identified that a subtype of mesothelioma may be a good candidate for a type of immunotherapy called anti-PD-L1.
Based on these findings, the researchers see genotyping of patients – where the precise genetic alterations that underlie their cancer are identified – as an important next step.
Dr. Bueno concludes:
“Even for a mutation that happens 1-2% of the time, it could mean the difference between life and death for a patient. We plan to continue this important research through investigator-sponsored trials evaluating the potential use of cancer immunotherapies for the treatment of mesothelioma.”
Genomic analysis is transforming the clinical landscape of cancer, bringing closer the day when individual patients are treated for their particular cluster of mutations – increasing the likelihood of a better prognosis.
Medical News Today recently reported on another example where, as a result of comprehensive genomic analyses, researchers concluded that pancreatic cancer is not one but four separate diseases and suggest that knowing which subtype of pancreatic cancer a patient has will allow doctors to give more accurate prognoses and treatment recommendations.