International Mesothelioma Program (IMP) at Brigham and Women’s Hospital

New, gender-specific mutations were discovered for the first time in a mesothelioma research study at the International Mesothelioma Program (IMP) at Brigham and Women’s Hospital. Studies have shown that women diagnosed with mesothelioma, typically have more favorable outcomes and a statistically better chance of survival than men with the same diagnosis. Identifying these different mutations and why women have an advantage are the first steps towards developing more effective treatments for everyone suffering from mesothelioma.

The study “Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma” was led by Assunta De Rienzo, PhD, co-director of the Thoracic Surgery Oncology Laboratory at BWH. It revealed that molecular differences may define the gender-specific outcomes observed in men and women. Findings from the study included results showing mutations in the TP53 gene, which is implicated in many types of cancers but not so much in mesothelioma, were twice as prevalent in female patients compared to male patients. Results also showed lower rates of BAP1 mutation in non-epithelioid tumors, a histological subtype associated with poor prognosis. Understanding these mutations begins with looking for genes that are mutated in more than one patient, and sets of commonly mutated genes that work together in “molecular pathways” within cancer cells.

Exploring the differences between mutations in men and women is paramount to learning how we can harness these differences and develop more personalized treatments. Pinpointing whether women have a genetic advantage based on molecular tumor properties involves identifying their mutations to answer a simple question: Do women have something in common among their cancers’ genes that can guide new mesothelioma treatments for men?

Examining the tumor genome as a whole and discovering and documenting genetic differences allows us to see how the mutations interact and will help provide targets for specific therapies. The estimated five-year survival for woman is 22% while for men it is 9%, and that gap widens even further when you look at the numbers for patients under the age of 50. This groundbreaking assessment of gender-specific mutations could lead to more individualized treatments that will benefit and improve outcomes for all patients, across the board.

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