E370: Single cell transcriptomic analysis of malignant peritoneal mesothelioma: finding the tumor cells?

Introduction: Malignant peritoneal mesothelioma (MPM) is a rare and understudied primary malignancy of the peritoneum. Patient typically present with advanced disease which plays a role in the morbidity and mortality associated with MPM. Current guidelines call for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for surgical candidates. Here we present the single cell transcriptomic analysis of two patients with MPM.

Methods: Patients were consented using IRB protocols for tissue collection. Ascites and tumor samples (peritoneum and omentum) were collected from patients. Samples were enzymatically dissociated (Miltenyi) to generate single cells suspensions. These were used to generate cDNA libraries (10X Genomics) that were sequenced followed by in-house pipeline processing of the data. Samples from two MPM patients (n=3 tissues) were compared to equivalent tissue from patients with Pseudomyxoma peritonei (PMP).

Results: Our single cell transcriptomic analysis reveals intra-tumoral heterogeneity amongst MPM patient’s tumors. Interestingly, MPM tumors lack a traditional tumor epithelial lineage as compared to other tumors of the gastrointestinal tract. Using inferCNV we demonstrate higher copy number variants (CNV) in the mesothelial cells of MPM tumors compared to other tumoral cellular lineages, placing them as the cell line responsible for tumor development. Last, we compared peritoneum and omentum from patients with MPM and PMP to show differences in the cellular and signaling pathways of their mesothelial cells.
 

 

Conclusions:

Using single cell transcriptomic analysis we provide a characterization of the tumor microenvironment of MPM tumors. Specifically, the cellular and signaling characterization of the tumor mesothelial cells of MPM patients.