Colin Collins, Ph.D.

Professor & Director, Laboratory for Advanced Genome Analysis, Vancouver Prostate Centre

加拿大不列颠哥伦比亚大学教授，高级基因组分析实验室(LAGA)主任，国际知名前列腺癌研究专家。1993年博士毕业于加拿大不列颠哥伦比亚大学，1998年任加利福利亚大学助理教授，2009年任不列颠哥伦比亚大学前列腺中心访问教授，2011年至今任职于不列颠哥伦比亚大学。成立华大基因和温哥华联合研究实验室等。主要研究将数学、基因组学、计算机科学和临床医学汇聚于诊断和治疗的转化基因组学。

BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma

Malignant peritoneal mesothelioma (PeM) is a rare and 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 exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis.
To search for novel therapeutic targets for PeM, we performed a comprehensive integrative multi-omics analysis of the genome, transcriptome, and proteome of 19 treatment-naïve PeM, and in particular, we examined BAP1 mutation and copy number status and its relationship to immune checkpoint inhibitor activation.
We found that PeM could be divided into tumors with an inflammatory tumor microenvironment and those without and that this distinction correlated with haploinsufficiency of BAP1. To further investigate the role of BAP1, we used our recently developed cancer driver gene prioritization algorithm, HIT’nDRIVE, and observed that PeM with BAP1 haploinsufficiency form a distinct molecular subtype characterized by distinct gene expression patterns of chromatin remodeling, DNA repair pathways, and immune checkpoint receptor activation. We demonstrate that this subtype is correlated with an inflammatory tumor microenvironment and thus is a candidate for immune checkpoint blockade therapies.
Our findings reveal BAP1 to be a potential, easily trackable prognostic and predictive biomarker for PeM immunotherapy that refines PeM disease classification. BAP1 stratification may improve drug response rates in ongoing phases I and II clinical trials exploring the use of immune checkpoint blockade therapies in PeM in which BAP1 status is not considered. This integrated molecular characterization provides a comprehensive foundation for improved management of a subset of PeM patients.