Malignant pleural mesothelioma affects men and women differently. One group of scientists now thinks there are many factors to explain this distinction, not just a few.
The researchers believe this understanding will be important to unlocking more of the mysteries of mesothelioma at the molecular level.
And that’s important because it is at the molecular level where next-generation mesothelioma treatment discoveries and diagnosis-improving breakthroughs are most likely to be found.
Writing in a recent issue of the journal Cancer Research, the scientists made note of the fact that malignant pleural mesothelioma attacks men much more often than it does women.
The researchers also noted that a woman who develops malignant pleural mesothelioma will probably long outlive a man who develops the cancer at around the same time.
Together, these two facts form one of the most frustrating questions about malignant pleural mesothelioma — why women are more resistant to the disease and biologically better equipped to fight it.
Mesothelioma Patients Studied on Molecular Level
To help them answer this riddle, the researchers conducted a molecular-level examination of 10 malignant pleural mesothelioma patients. These patients were a mix of men and women.
The starting point was the collection of mesothelioma tumor specimens from each patient. The specimens were then subjected to whole-genome sequencing.
In the course of this sequencing, the researchers took care to set aside control samples. They did this to permit identification of genes that might be capable of causing other genes to mutate — “driver genes,” they’re called.
Pinpointing potential mutation-causing drivers was important because they are thought to be an underlying trigger of malignant pleural mesothelioma.
With the sequencing completed, the researchers then began uncovering molecular differences between the men and women patients.
They also discovered molecular differences among the histology of the harvested tumors. Specifically, single-nucleotide variants of BAP1 were observed in 21 percent of cases.
BAP1 is the name of a gene that controls other important genes. When BAP1 mutates, it becomes inactive.
This inactivity is what is widely thought to allow mesothelioma to onset. BAP1 has been shown by other research to mutate following exposure to asbestos fibers.
Meanwhile, in this latest research, lower mutation rates were observed in the sarcomatoid type of malignant pleural mesothelioma tumor sample.
Interesting Discoveries Regarding Mesothelioma Survival
The scientists also observed differences among the sexes in regard to the loss of chromosome 22q.
Also, shorter mesothelioma survival seemed to be associated with men who had deletion of the enzyme CDKN2A. This was particularly true for men who did not have the epithelioid mesothelioma tumor type.
The women in the study cohort more often had mutations of gene TP53 than did the men. Also, novel mutations were found in genes MYH9 and RHOA, which are associated with the integrin-linked kinase pathway.
Finally, expression levels of BAP1, MYH9 and RHOA were found to be significantly higher in non-epithelioid tumors, the researchers revealed.
Higher BAP1, MYH9 and RHOA expression levels also were linked to a significant reduction in survival of the entire cohort and across gender subgroups, the researchers added.
“Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appears to drive malignant pleural mesothelioma,” the authors wrote.
The title of the article is “Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma.”
The authors were from Brigham and Women’s Hospital and Harvard Medical School, Massachusetts General Hospital, Dana-Farber Cancer Institute and Harvard School of Public Health, Malaysian Genomics Resource Centre and Baylor College of Medicine.