On February 29th, Nature Genetics published the results of a comprehensive mesothelioma gene-sequencing study conducted by our team of researchers at the International Mesothelioma Program (IMP) at Brigham and Women’s Hospital and scientists from Genentech. This seminal study provides new genetic insight into mesothelioma and offers a broader understanding of the disease’s mutation patterns. Through a comprehensive genomic analysis of over 200 mesothelioma tumors, our team of researchers identified several previously unknown genetic mutations and recurrent mutations within mesothelioma. The results prove the validity of sequencing mesothelioma tumors in the same way other forms of cancer are sequenced to determine targeted therapies. This study is the largest genetic analysis of mesothelioma thus far and could be a game-changer for identifying better targeted treatments.
Some of the mutations identified in our study have been previously found in other cancers and can be targeted by existing drugs. Our researchers also identified that while the mutational signature for mesothelioma is different than most other cancers, it does closely resemble that of ovarian cancer. While these mutations may only occur in a very small fraction of mesothelioma tumors, if identified, they can still be used to pinpoint existing drug therapies for mesothelioma patients. The current 5-year survival rate for patients with a mesothelioma diagnosis rests between 5% and 10%, so even this small percentage can be a beacon of hope for our patients at the IMP.
This new possibility of identifying actionable mutations that can be targeted by existing therapies should lead us to sequencing all tumors of mesothelioma patients, despite previous theories stating that doing so was pointless. Additionally, these previously unidentified genetic mutations can help improve our methods of diagnosing and screening for mesothelioma. Overall, we looked at 216 malignant pleural mesothelioma (MPM) samples to compare the DNA and RNA from healthy tissue to cancerous tissue and found over 2,500 alterations, identifying 10 significantly mutated genes.
This large number of alterations may be able to serve as improved markers for diagnosing mesothelioma earlier and enabling pathologists to better predict patient outcomes. The findings from this study have big implications for our next steps here at the IMP. Genotyping patients, the practice of looking for genetic differences at exact locations in the genome, could now become a routine part of screening and forming a plan for treatment.
The mortality rate for mesothelioma is very high and this discovery of treatable mutations within this disease could be the difference between life and death for a new group of our patients. Our research will continue as we work to examine the potential use for cancer immunotherapies in the treatment of mesothelioma.
Disclaimer: The content of this blog post is for general educational purposes only and is not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment. This blog post should not be interpreted as an endorsement by Dr. Bueno or the blog’s sponsor.