BAP1 Loss Predicts Therapeutic Vulnerability in Malignant Peritoneal Mesothelioma

Shrestha, R.; Nabavi, N.; Lin, Y.-Y.; Mo, F.; Anderson, S.; Volik, S.; Adomat, H. H.; Lin, D.; Xue, H.; Dong, X.; Shukin, R.; Bell, R. H.; McConeghy, B.; Haegert, A.; Brahmbhatt, S.; Li, E.; Oo, H. Z.; Hurtado-Coll, A.; Fazli, L.; Zhou, J.; McConnell, Y.; McCart, A.; Lowy, A.; Morin, G. B.; Daugaard, M.; Sahinalp, S. C.; Hach, F.; Le Bihan, S.; Gleave, M. E.; Wang, Y.; Churg, A.; Collins, C. C.

doi:10.1101/243477

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bioRxiv · 10.1101/243477

BAP1 Loss Predicts Therapeutic Vulnerability in Malignant Peritoneal Mesothelioma

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Abstract

BackgroundMalignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM yet exist. In the search for novel therapeutic target candidates in PeM, we performed a comprehensive integrative multi-omics analysis of 19 treatment-naive PeM tumors.\n\nResultsThe analysis identified PeM tumors with BAP1 loss to form a distinct molecular subtype characterized by distinct expression patterns of genes involved in chromatin remodeling, DNA repair pathway, and immune checkpoint receptor activation. This PeM subtype could potentially benefit from immune checkpoint, PARP, or HDAC inhibition therapies.\n\nConclusionsOur findings uncover BAP1 as a trackable prognostic and predictive biomarker, and refine PeM disease classification. This integrated molecular characterization provides a comprehensive foundation for developing PeM precision medicine.

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Shrestha, R., Nabavi, N., Lin, Y.-Y., Mo, F., Anderson, S., Volik, S., Adomat, H. H., Lin, D., Xue, H., Dong, X., Shukin, R., Bell, R. H., McConeghy, B., Haegert, A., Brahmbhatt, S., Li, E., Oo, H. Z., Hurtado-Coll, A., Fazli, L., Zhou, J., McConnell, Y., McCart, A., Lowy, A., Morin, G. B., Daugaard, M., Sahinalp, S. C., Hach, F., Le Bihan, S., Gleave, M. E., Wang, Y., Churg, A., Collins, C. C.. 2018-03-15. BAP1 Loss Predicts Therapeutic Vulnerability in Malignant Peritoneal Mesothelioma. https://doi.org/10.1101/243477

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