A comprehensive review published in the journal Frontiers in Oncology has revealed that rather than being a single disease, mesothelioma comprises multiple distinct genetic subtypes. This finding explains why some patients respond well to treatments while others don’t, and why the asbestos-related cancer behaves so differently in different people.
Mesothelioma Discovery Shows that Each Diagnosis Can Have a Very Different Biology
Researchers from Mount Sinai Hospital and Columbia University Irving Medical Center in New York, and the University Hospital of Wales and School of Medicine, Cardiff University in the United Kingdom reviewed recent discoveries about mesothelioma genetics and found that, while all mesotheliomas are aggressive cancers affecting the lining around body cavities, they differ dramatically in their underlying genetic mutations, the behavior of the tumors, and the way they respond to treatment.
The researchers found that pleural mesothelioma represents approximately 85-90% of mesothelioma diagnoses, while about 15% are in the peritoneum and less than 1% are in the pericardium or tunica vaginalis. Each location tends to have different genetic characteristics, with most mesotheliomas characterized by mutations in tumor suppressor genes. These are the cellular brakes that normally prevent cancer but stop working when mutated. The most frequently altered genes include BAP1 (found in 44-53% of mesotheliomas), CDKN2A (25-49%), MTAP (27-34%), and NF2 (21-33%). These mutations affect how cells grow, divide, and respond to DNA damage.
Genetic Testing Can Guide Mesothelioma Treatment and Predict Outcomes
The genetic profiles of each mesothelioma tumor type differ, with epithelioid (the most common and least aggressive subtype) having BAP1 alterations in 51-59% of cases, while sarcomatoid (the most aggressive subtype) has BAP1 alterations in only 17-25% but CDKN2A alterations in approximately 80% of cases. The study also identified several rare genetic subtypes that behave very differently from typical cases.
Some mesotheliomas have specific gene fusions—like ALK rearrangements found in rare peritoneal cases, particularly in young women. These mesotheliomas can be treated with targeted drugs called ALK inhibitors that specifically block the abnormal protein created by the fusion, offering hope for personalized treatment approaches. Other rare subtypes include those with genomic near-haploidization (where cells lose nearly half their chromosomes), EWSR1::ATF1 fusions, and EWSR1::YY1 fusions—each representing distinct diseases requiring different treatment strategies.
This mesothelioma research explains why “one-size-fits-all” treatments don’t work equally well for all patients and underscores the importance of comprehensive genetic testing to guide personalized treatment decisions. It can help distinguish mesothelioma from benign condition; predict how aggressively a patient’s mesothelioma will be; and identify the treatments most likely to work, all based on the tumor’s genetic profile.
If you or someone you love has been diagnosed with mesothelioma, the Patient Advocates at Mesothelioma.net are here to help. Contact us today at 1-800-692-8608 to learn more.
