Publication

Transcriptomic plasticity is a hallmark of metastatic pancreatic cancer

Authors: Alejandro Jiménez-Sánchez, Sitara Persad, Akimasa Hayashi, Shigeaki Umeda, Roshan Sharma, Yubin Xie, Arnav Mehta, Wungki Park, Ignas Masilionis, Tinyi Chu, Feiyang Zhu, Jungeui Hong, Ronan Chaligne, Eileen M. O’Reilly, Linas Mazutis, Tal Nawy, Itsik Pe’er, Christine A. Iacobuzio-Donahue, Dana Pe’er
Journal: Biorxiv
Atlas: Memorial Sloan Kettering Cancer Center

Abstract

Metastasis is the leading cause of cancer deaths; nonetheless, how tumor cells adapt to vastly different organ contexts is largely unknown. To investigate this question, we generated a transcriptomic atlas of primary tumor and diverse metastatic samples from a patient with pancreatic ductal adenocarcinoma who underwent rapid autopsy. Unsupervised archetype analysis identified both shared and site-specific gene programs, including lipid metabolism and gastrointestinal programs prevalent in peritoneum and stomach wall lesions, respectively. We developed a probabilistic approach for inferring clonal phylogeny from single-cell and matched whole-exome data. Distantly related genetic clones in the peritoneum express the lipid metabolism program, likely due to signaling by the adipocyte-rich peritoneum environment, and cells in most clones express multiple programs, suggesting that transcriptomic plasticity is a prevalent feature of metastatic cells. These deeply annotated analyses using a patient-centric platform provide a model for investigating metastatic mechanisms and plasticity in advanced cancer.


Data Availability
FilesCRDC-GC/SB-CGC (dbGaP )Synapse (Open Access )
scRNA-seq Level 2540
scRNA-seq Level 302
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Filename
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Publications
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Assay
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Data Access
Metadata
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