Related Experiment Video
Updated: Oct 16, 2025
08:01
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
2.0K
Molecular Characterization of Peritoneal Mesotheliomas
Michael Offin1, Soo-Ryum Yang2, Jacklynn Egger1
1Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
Summary
Malignant peritoneal mesothelioma (MPeM) exhibits unique genomic features, with common alterations in BAP1, NF2, SETD2, and TP53. BAP1 alteration or loss is linked to poorer survival in MPeM patients.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Malignant peritoneal mesothelioma (MPeM) is a rare cancer with distinct clinical and biological characteristics compared to malignant pleural mesothelioma.
- Limited genomic and immunophenotypic data are available for MPeM, hindering targeted therapeutic development.
Purpose of the Study:
- To comprehensively characterize the genomic and immunophenotypic landscape of malignant peritoneal mesothelioma.
- To identify potential biomarkers for prognosis and therapeutic targets in MPeM.
Main Methods:
- Prospective collection of 50 MPeM tumor samples for genomic analysis using next-generation sequencing (NGS).
- Assessment of genomic near-haploidization (GNH).
- Immunohistochemistry (IHC) evaluation of WT1, BAP1, mesothelin, VISTA, and programmed death-ligand 1 (PD-L1).
- Correlation of genomic and IHC features with overall survival.
Main Results:
- Commonly observed genomic alterations include BAP1 (60%), NF2 (24%), SETD2 (22%), and TP53 (16%).
- Genomic near-haploidization (GNH) was identified in 8% of assessable specimens.
- High IHC positivity rates for mesothelin (93%), WT1 (96%), VISTA (89%), and PD-L1 (50%).
- BAP1 alteration or loss, identified by NGS and IHC, was associated with significantly shorter overall survival (43.8 vs. 117.3 months, p=0.04).
- Pathogenic germline variants were detected in 3 of 30 patients (POT1, MUTYH, BAP1).
Conclusions:
- MPeM possesses a distinct genomic profile characterized by frequent BAP1, NF2, TP53, and SETD2 alterations.
- BAP1 alteration/loss serves as a potential prognostic biomarker for reduced survival in MPeM.
- A subset of MPeM patients harbor GNH, suggesting complex genomic instability.
- The findings provide critical insights into MPeM biology, paving the way for novel therapeutic strategies.
