الفهرس 
Malignant Pleural MesotheliomaOnly 14 pages are availabe for public view
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Abstract
Malignant Pleural Mesothelioma (MPM) is a lethal and rare cancer linked to asbestos exposure. The median overall survival of MPM is estimated to be 1 year and the cure is rarely occurred. Up till now little is known about the prognostic and predictive factors as well as the mechanisms of resistance to conventional therapy of the disease.
The exact biology and molecular mechanisms of mesothelioma is still poorly understood. Although, current treatment modalities may improve the quality of life, they have shown modest effect in improving the overall survival and novel treatments are still needed.
Investigating the genomic nature of Malignant Mesothelioma may identify novel molecular targets for therapy for this rarely cured disease.
Three independent and significantly mutated genes (BAP1, CDKN2A/B loss NF2) have been identified and reported to be involved in MPM oncogenesis. from the three identified genetic alterations of MPM, BRCA Associated Protein 1 (BAP1) was the most common mutated gene.
Many studies have focused on the study of BAP1 gene and the types of mutations that occur in it and its effect on Prognosis and the survival of MPM patients but did not study the full prognostic picture and the relationship of the BAP1 gene mutation and its impact on all the all clinicopathological characteristics, survival and the response to treatment. In addition the results of these published studies are controversy.
The current study was designed to assess the frequency of BAP1 mutation in Egyptian patients with Advanced Sporadic MPM. Then it analyzed the full prognostic picture of BAP1 mutation on MPM patients, not only its association with Overall Survival (OS) but also with clinical response to chemotherapy, Progression Free Survival (PFS) after first and second line chemotherapy, and other clinicopathological characteristics (Age, Gender, Asbestos Exposure, Smoking, Histology, Stage of the disease, Occupation and Metastasis).
It also investigates if that will open a new era for discovering a novel lethal target in the setting of BAP1.
The study was a prospective, cohort study conducted on 122 patients who was eligible and newly diagnosed with Advanced MPM at the outpatient chest clinic, National Cancer Institute (NCI), Cairo University during the period from March 2013 to the end of May 2016. Then these patients were categorized into 2 groups (BAP1 mutated and BAP1 non mutated groups) according to Polymerase Chain Reaction (PCR) and Sequencing results.
The current study showed that:-
• About 38.5% of patients with Advanced Sporadic MPM have BAP1 mutations and 14 different BAP1 somatic mutations have been identified so far (4 missense mutations, 3 nonsense mutations, 6 deletions and 1 insertion).
• Regarding the relation between BAP1 mutation and Clinicopathological characteristics, it was found that there was a statistically significant relation between the presence of mutation (s) in BAP1 gene and incidence of organ metastasis (Brain, bone and liver metastasis). On the other hand, a trend towards significant relation was found between the presence of mutation (s) in BAP1 gene and the stage of the disease and occupation (p=0.08). There was no significant relation between BAP1 gene and other Clinicopathological features of the patient including Age, Gender, Asbestos Exposure, Smoking, Histology and other Metastasis types (Supraclavicular Lymph Node and Lung Metastasis).
• There were no significant associations between BAP1 mutation and PFS (P = 0.31), clinical response (p =0.34) after first line treatment and OS (P = 0.67). There were significant associations between BAP1 mutation and PFS (p = 0.046) and clinical response (p = 0.017) after second line treatment where BAP1 mutation associate with shorter PFS and poor clinical response.
As a conclusion BRCA Associated Protein 1 (BAP1) gene mutations are relatively common in Egyptian patients with Advanced Sporadic Malignant Pleural Mesothelioma (MPM). BAP1 gene mutation is associated with disease progression especially after second line treatment. It has no significant effect on clinicopathological variables except for occurrence of organ metastasis where it is associated with the occurrence of organ metastasis.