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Published on: April 21, 2022
Well-Differentiated Papillary Mesothelioma of the Peritoneum Is Genetically Distinct from Malignant Mesothelioma
Raunak Shrestha1,2,3, Noushin Nabavi1,4, Stanislav Volik1
1Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada.
Abstract:
Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process and, if neoplastic, whether it is a variant or precursor of epithelial malignant mesothelioma or is a different entity. Using whole exome sequencing of five WDPMs of the peritoneum, we have identified distinct mutations in EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 shared by WDPM cases but not reported in malignant mesotheliomas. Furthermore, we show that WDPM is strongly enriched with C > A transversion substitution mutations, a pattern that is also not found in malignant mesotheliomas. The WDPMs lacked the alterations involving BAP1, SETD2, NF2, CDKN2A/B, LASTS1/2, PBRM1, and SMARCC1 that are frequently found in malignant mesotheliomas. We conclude that WDPMs are neoplasms that are genetically distinct from malignant mesotheliomas and, based on observed mutations, do not appear to be precursors of malignant mesotheliomas.
Insights
Well-differentiated papillary mesothelioma (WDPM) is a distinct neoplasm, not a reactive process or precursor to malignant mesothelioma. Genetic analysis reveals unique mutations in WDPM, differentiating it from malignant mesothelioma.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation often found incidentally in the peritoneum.
- Its classification as a neoplasm or reactive process, and its relationship to malignant mesothelioma, remain debated.
Purpose of the Study:
- To genetically characterize WDPM and determine its relationship to malignant mesothelioma.
- To resolve the controversy regarding the neoplastic or reactive nature of WDPM.
Main Methods:
- Whole exome sequencing was performed on five peritoneal WDPM samples.
- Genetic alterations in WDPM were compared to those typically found in malignant mesotheliomas.
Main Results:
- WDPM samples exhibited distinct mutations in genes including EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73.
- A unique mutational signature (C > A transversions) was observed in WDPM, absent in malignant mesotheliomas.
- WDPM lacked common malignant mesothelioma mutations in genes like BAP1, SETD2, and NF2.
Conclusions:
- WDPM represents a neoplastic entity genetically distinct from malignant mesothelioma.
- Based on genetic profiles, WDPM does not appear to be a precursor to malignant mesothelioma.
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