Transcriptomic plasticity is a hallmark of metastatic pancreatic cancer

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 Mažutis; Tal Nawy; Itsik Pe’er; Christine A Iacobuzio-Donahue; Dana Pe'er

doi:10.1158/0008-5472.CAN-25-1117

Title	Transcriptomic plasticity is a hallmark of metastatic pancreatic cancer
Authors	Jiménez-Sánchez, Alejandro ; Persad, Sitara ; Hayashi, Akimasa ; Umeda, Shigeaki ; Sharma, Roshan ; Xie, Yubin ; Mehta, Arnav ; Park, Wungki ; Masilionis, Ignas ; Chu, Tinyi ; Zhu, Feiyang ; Hong, Jungeui ; Chaligne, Ronan ; O’Reilly, Eileen M ; Mažutis, Linas ; Nawy, Tal ; Pe’er, Itsik ; Iacobuzio-Donahue, Christine A ; Pe'er, Dana
DOI	10.1158/0008-5472.CAN-25-1117
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Is Part of	Cancer research.. Philadelphia : American Association for Cancer Research (AACR). 2025, Early Access, p. [1-59].. ISSN 0008-5472. eISSN 1538-7445
Keywords [eng]	cancer metastasis ; single-cell transcriptomics ; tumor cell plasticity
Abstract [eng]	Metastasis is the leading cause of cancer deaths. To develop strategies for intercepting metastatic progression, a better understanding of how tumor cells adapt to vastly different organ contexts is needed. To investigate this question, a single-cell transcriptomic atlas of primary tumor and diverse metastatic samples (liver, omentum, peritoneum, stomach wall, lymph node, and diaphragm) from a patient with pancreatic ductal adenocarcinoma who underwent rapid autopsy was generated. Using unsupervised archetype analysis, both shared and site-specific gene programs were identified, including lipid metabolism and gastrointestinal programs prevalent in peritoneal and stomach wall lesions, respectively. We developed PICASSO as a probabilistic approach for inferring clonal phylogeny from single-cell and matched whole-exome sequencing data. Comparison of PICASSO-generated clonal structure with phenotypic signatures revealed that pancreatic cancer cells adapted to local environments with minimal contribution from clonal genotype. Our results suggest a paradigm whereby strong environmental effects are imposed on highly plastic cancer cells during metastatic dissemination.
Published	Philadelphia : American Association for Cancer Research (AACR)
Type	Journal article
Language	English
Publication date	2025
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„Transcriptomic plasticity is a hallmark of metastatic pancreatic cancer“