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Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas.

ABSTRACT: In leiomyosarcoma (LMS), a very aggressive disease, a relatively transcriptionally uniform subgroup of well-differentiated tumors has been described and is associated with poor survival. The question raised how differentiation and tumor progression, two apparently antagonist processes, coexist and allow tumor malignancy. We first identified the most transcriptionally homogeneous LMS subgroup in three independent cohorts, which we named 'hLMS'. The integration of multi-omics data and functional analysis suggests that hLMS originate from vascular smooth muscle cells and show that hLMS transcriptional program reflects both modulations of smooth muscle contraction activity controlled by MYOCD/SRF regulatory network and activation of the cell cycle activity controlled by E2F/RB1 pathway. We propose that the phenotypic plasticity of vascular smooth muscle cells coupled with MYOCD/SRF pathway amplification, essential for hLMS survival, concomitant with PTEN absence and RB1 alteration, could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness.

SUBMITTER: Darbo E

PROVIDER: S-EPMC9856933 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas.

Darbo Elodie E Pérot Gaëlle G Darmusey Lucie L Le Guellec Sophie S Leroy Laura L Gaston Laëtitia L Desplat Nelly N Thébault Noémie N Merle Candice C Rochaix Philippe P Valentin Thibaud T Ferron Gwenaël G Chevreau Christine C Bui Binh B Stoeckle Eberhard E Ranchere-Vince Dominique D Méeus Pierre P Terrier Philippe P Piperno-Neumann Sophie S Collin Françoise F De Pinieux Gonzague G Duffaud Florence F Coindre Jean-Michel JM Blay Jean-Yves JY Chibon Frédéric F

Cancers 20230115 2

In leiomyosarcoma (LMS), a very aggressive disease, a relatively transcriptionally uniform subgroup of well-differentiated tumors has been described and is associated with poor survival. The question raised how differentiation and tumor progression, two apparently antagonist processes, coexist and allow tumor malignancy. We first identified the most transcriptionally homogeneous LMS subgroup in three independent cohorts, which we named 'hLMS'. The integration of multi-omics data and functional a ...[more]

PMID: 36672483

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Dataset Information

Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas.

Publications

Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas.

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