ArticleNature genetics2026
Clonal heterogeneity in human pancreatic ductal adenocarcinoma and its impact on tumor progression.
Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Melanoma evolution in the lymph node shapes systemic outcomes.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
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Authors and funding
30 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer characterized by profound desmoplasia and cellular heterogeneity, which cannot be fully resolved using traditional bulk sequencing approaches. To understand how this heterogeneity contributes to PDAC biology, we analyzed a large cohort of primary tumors (n = 62) profiled using single-cell RNA sequencing (443,451 single cells), including a subset of 11 tumors with matched spatial transcriptomics (53,236 spots), to map clonal, transcriptional and spatial diversity. Moreover, our sample set includes a unique cohort of matched samples from six tumors collected before and after treatment with chemotherapy. Our analysis revealed notable intratumoral heterogeneity, with multiple genetically distinct neoplastic clones coexisting within individual tumors. We observed clone-specific ligand-receptor programs that are modulated by genomic dosage: amplifications of ligands or receptors enriched corresponding interactions, while deletions suppressed them, with genetically encoded differences supported by spatial transcriptomics and multiplex immunofluorescence. Phylogenetic integration identified focal 8q24 (MYC) amplification as recurrently associated with classical-to-basal transitions occurring within tumor lineages at a frequency above chance; these transitions were accompanied by coordinated depletion of immune-response programs. Functional perturbation experiments in murine and primary human models showed that MYC knockdown reactivates classical transcriptional programs and restores immune-response pathways, supporting a role for MYC in maintaining a basal, immune-depleted state. Spatial analyses further revealed dispersed clones enriched for epithelial-to-mesenchymal transition activity and immune suppression, correlating with metastatic potential and colonization of lymph node niches. These dispersed clones shifted toward a basal phenotype, contributing to disease progression. Our findings highlight the critical role of clonal diversity, transcriptional plasticity and tumor microenvironment interactions in shaping human PDAC biology. This work provides a detailed view of the molecular and spatial heterogeneity of PDAC and offers potential avenues for therapeutic intervention targeting clonal evolution and the mechanisms driving metastasis.
Identifiers
42869988What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.