Article : The Effect Of BAP1 Gene Mutations On Platinum-induced Double-strand Breaks (DSBs) In Egyptian Patients With Malignant Pleural Mesothelioma (MPM)

Title

The Effect Of BAP1 Gene Mutations On Platinum-induced Double-strand Breaks (DSBs) In Egyptian Patients With Malignant Pleural Mesothelioma (MPM)

Author

Raghda Shehab El-Din, Nagwa Ali Sabri, Abeer A Bahnasy, Ahmed El Bastawisy

Background: Malignant Pleural Mesothelioma (MPM) is a rare but highly lethal tumor with limited therapeutic options.  Patients with MPM have a poor prognosis, with estimated 1 year median survival and rare cure. The BRCA associated protein 1 (BAP1) has the highest prevalence of protein-altering mutations identified in MPM. Platinum based chemotherapy is one of the first line therapies for MPM. It works on tumor cells by induction of DNA Double-strand breaks.   Objective: Assessment of the effect of BAP1 gene mutations on platinum-induced DNA Double-strand breaks (DSBs) in Egyptian patients with malignant Pleural mesothelioma.   Methods: A prospective, cohort study was conducted on patients who were diagnosed and treated as advanced MPM.  BAP1 gene mutations were assessed from circulating tumor cells (CTCs) in the blood by polymerase chain reaction (PCR) and sequencing. The relationship between BAP1 gene mutations, and clinical response to platinum based chemotherapy was assessed using chi-square test.   Results: From the 122 patients assessed, 47 (38.5%) MPM cases showed one or more mutations in BAP1 gene. No statistically significant difference was found between patients with or without BAP1 gene mutation and the overall clinical benefit after Platinum based chemotherapy.   Conclusion: BAP1 gene mutations are relatively common in Egyptian patients. BAP1 mutations don’t affect the sensitivity of MPM tumor cells to the effect of platinum-induced Double-strand breaks (DSBs).

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