BAP1 gene mutations in Egyptian patients with advanced sporadic malignant pleural mesothelioma (MPM): relation with clinical outcomes and survival

Our plain-English summary of BAP1 gene mutations in Egyptian patients with advanced sporadic malignant pleural mesothelioma (MPM): relation with clinical outcomes and survival, by A.A. Bahnasy, R.S. El-Din, N.A. Sabri, et al (Cancer Genetics, 2018).

The study

• Authors: A.A. Bahnasy, R.S. El-Din, N.A. Sabri, C.A. Abdel-Rahman, A.E. Bastawisy
• Journal: Cancer Genetics
• Published: 2018;228-229:83-92
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant Pleural Mesothelioma (MPM) is a lethal cancer with few therapeutic options. Patients with MPM have a poor prognosis, with estimated 1 year median survival and currently no treatment is curative. The BRCA associated protein 1 (BAP1) has the highest prevalence of protein-altering mutations identified in MPM.

Aims: Assessment of the frequency and pattern of BAP1 gene mutations in Egyptian patients with advanced sporadic MPM in relation to disease progression and survival rates in order to identify a novel therapeutic target for MPM.

Methods: This prospective, cohort study included 122 patients who were diagnosed and treated as advanced MPM. BAP1 gene mutations were assessed from circulating tumor cells (CTCs) by polymerase chain reaction (PCR) and sequencing and these mutations have been confirmed using the tumor tissue. BAP1 immunohistochemistry was performed using the Dako Envision visualization system. The relationship between BAP1 gene mutations, PFS and OS rates was assessed using the log rank test. The relationship between BAP1 gene mutations, clinical response and patient's clinicopathological characteristics was assessed using chi-square test.

Results: Forty seven (38.5%) MPM cases showed one or more mutations in BAP1 gene. The presence of BAP1 mutations associated significantly with BAP1 protein expression (p < 0.001), the incidence of organ metastasis (p = 0.04), PFS after second line treatment (p = 0.04) and clinical response after second line treatment (p = 0.01) only.

Conclusion: BAP1 gene mutations are relatively common in Egyptian patients with advanced sporadic MPM. BAP1 mutations are associated with disease progression especially after second line therapy and the incidence of organ metastasis.

Copyright © 2018 Elsevier Inc. All rights reserved.

In plain English

This prospective cohort study followed 122 patients with advanced sporadic malignant pleural mesothelioma (MPM) treated at the National Cancer Institute, Cairo University, Egypt, from March 2013 to May 2016. The authors tested circulating tumor cells in blood, and tumor tissue, for mutations in the BAP1 gene, and stained tissue for BAP1 protein. Of 119 patients with information, 51 reported a history of asbestos exposure. The blood test found BAP1 mutations in 47 patients (38.5%), and the tissue test in 40 (32.8%). Patients with mutations more often lacked BAP1 protein. They also more often had cancer spread to organs such as brain, bone and liver (34% compared with 16.7%). After second-line chemotherapy, fewer patients with mutations showed clinical benefit (10% compared with 37.5%). Their median time before the disease progressed was shorter (2.5 compared with 6.3 months). Mutations were not significantly linked to overall survival, to first-line treatment results, or to asbestos exposure. The authors concluded that BAP1 mutations are relatively common in these patients and are associated with disease progression, especially after second-line treatment. They recommended studies of larger numbers of patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective cohort study (genetic testing of blood and tumor tissue, with follow-up of treatment response and survival)
• Who was studied: 122 patients (63 women, 59 men, aged 21 to 81) diagnosed with and treated for advanced (stage III or IV) malignant pleural mesothelioma at the National Cancer Institute, Cairo University, Egypt, March 2013 to May 2016
• Exposure: The main factor studied was BAP1 gene mutation status, not asbestos. A history of asbestos exposure was reported by 51 of 119 patients (42.9%), and 13 of 46 patients with occupation data (28.3%) had occupationally linked MPM. No fiber types, products or doses were given.
• Main results:
  • BAP1 mutations were found in 47 of 122 patients (38.5%) by testing circulating tumor cells, and in 40 patients (32.8%) by testing tumor tissue. The authors found no significant difference between the two methods (p=0.1).
  • BAP1 mutations were significantly associated with absence of BAP1 protein (P < 0.001). Protein was absent in 40 of 47 patients (85%) with mutations and in 9 of 75 patients (12%) without mutations.
  • Organ metastasis (to brain, bone and liver) occurred in 16 of 47 patients (34%) with BAP1 mutations and in 12 patients (16.7%) without mutations. The text gives 12/75 and p = 0.04; the table gives 12 of 72 and p 0.045.
  • After second-line treatment, 10% of patients with BAP1 mutations showed clinical benefit (complete response, partial response or stable disease), compared with 37.5% of patients without mutations (p = 0.01). The table gives 3 of 30 and 12 of 32 patients.
  • Median progression-free survival after second-line treatment was 2.5 months in patients with BAP1 mutations and 6.3 months in those without (P = 0.04).
  • After first-line treatment, median progression-free survival was 8 months in both groups (p = 0.3). Clinical benefit was 56.5% with mutations versus 46.2% without (p = 0.3), not statistically significant.
  • Overall survival did not differ significantly between patients with and without BAP1 mutations (p = 0.67); it was about 12.4 months in both groups.
  • BAP1 mutations were not significantly related to asbestos exposure. Exposure was reported by 21 of 47 patients (44.7%) with mutations and 30 of 72 (41.7%) without (table p value 0.85). Mutations were also not significantly related to age, gender, smoking or histologic subtype.
  • Across all patients, histologic subtype was significantly related to overall survival (p = 0.01): epitheloid 12.331 months, biphasic 12.166 months, sarcomatoid 3.594 months. Asbestos exposure was not significantly related to median overall survival.
• The authors' conclusion: The authors concluded that BAP1 gene mutations are relatively common in Egyptian patients with advanced sporadic MPM and are associated with disease progression, especially after second-line treatment. Apart from organ metastasis, they found no significant relation with clinicopathological variables.
• Limitations the authors state:
  • The authors recommended assessing larger numbers of MPM patients to draw definitive conclusions about the prognostic effect of BAP1.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: BAP1, Pleural Mesothelioma, Prognosis, Median Survival, Disease Progression, Cohort Study, Immunohistochemistry, Metastasis.

Related studies

• High Incidence of Somatic BAP1 alterations in sporadic malignant mesothelioma — M. Nasu, M. Emi, et al. (2015)
• Genomic profiling of the genes on chromosome 3p in sporadic clear cell renal cell carcinoma — Y. Togo, Y. Yoshikawa, et al. (2016)
• Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases — A. Rusch, G. Ziltener, et al. (2015)
• Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma — S. Sneddon, J.S. Leon, et al. (2015)
• Tumours associated with BAP1 mutations — R. Murali, T. Wiesner, et al. (2013)
• Germline BAP1 mutations induce a Warburg effect — A. Bononi, H. Yang, et al. (2017)

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