ArticleGenome medicine2021
Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Multi-sampling allows intra-tumoral heterogeneity querying and vulnerability profiling in glioblastoma.Neuro-oncology · 2026Article
- Multiplexed Transcriptomics for Screening Drug Combinations and Defining the Mechanism of Action of HCC Therapeutics at Single-Cell Resolution.Cell proliferation · 2026Article
- Metabolic vulnerabilities in pleural mesothelioma.Oncogenesis · 2026Review
- Multiomics and multi-region spatial transcriptome analysis reveal cellular networks and pathways associated with HCC recurrence.JHEP reports : innovation in hepatology · 2026Article
- Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Multiomic, Histologic, and scRNA-seq Profiling of Pleural Mesothelioma Reveals Negative Prognosis Associated With a Novel Uncommitted Molecular Phenotype.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Methylation biomarkers can distinguish pleural mesothelioma from healthy pleura and other pleural pathologies.Molecular oncology · 2026Article
- Multi-omics integration in malignant pleural mesothelioma: from molecular evolution and immune ecosystems to precision therapy.Frontiers in oncology · 2026Review
- Review
- Review
- De novo pyrimidine synthesis is a collateral metabolic vulnerability in NF2-deficient mesothelioma.EMBO molecular medicine · 2025Article
- Pleural mesothelioma.Nature reviews. Disease primers · 2025Review
- Exploration and Application of Malignant Cell Heterogeneity Analysis with Single-Cell Transcriptome Sequencing Technology.Aging and disease · 2025Review
- Review
- Mesothelioma cell heterogeneity identified by single cell RNA sequencing.Scientific reports · 2025Article
- Article
- Advances in diagnosis and management of pleural mesothelioma: the Danish clinical guidelines.European clinical respiratory journal · 2025Review
- Genome-wide DNA methylation analysis reveals a unique methylation pattern for pleural mesothelioma compared to healthy pleura and other lung diseases.Clinical epigenetics · 2024Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMalignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples.
methodsIntra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic, or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed.
resultsSequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed the contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment, were observed and led to a switch from a hot to a cold immune profile in three patients.
conclusionsThis comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic, and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support the need for multi-sampling for the implementation of molecular-based precision medicine.
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