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Complex Elucidation of Cells-of-Origin in Pediatric Soft Tissue Sarcoma: From Concepts to Real Life, Hide-and-Seek through Epigenetic and Transcriptional Reprogramming

期刊

出版社

MDPI
DOI: 10.3390/ijms23116310

关键词

sarcoma; soft tissue sarcoma; transcriptional networks; cellular reprogramming; transdifferentiation; cell-of-origin; epigenetics; tumor heterogeneity; clinical management

资金

  1. Fondation de France institution

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This article discusses how cellular reprogramming mediated by driver genes in soft tissue sarcoma can reshape the characteristics of transformed cells and emphasizes the importance of the epigenetic context of genetic alterations in the initiation and progression of tumors.
Soft tissue sarcoma (STS) comprise a large group of mesenchymal malignant tumors with heterogeneous cellular morphology, proliferative index, genetic lesions and, more importantly, clinical features. Full elucidation of this wide diversity remains a central question to improve their therapeutic management and the identity of cell(s)-of-origin from which these tumors arise is part of this enigma. Cellular reprogramming allows transitions of a mature cell between phenotypes, or identities, and represents one key driver of tumoral heterogeneity. Here, we discuss how cellular reprogramming mediated by driver genes in STS can profoundly reshape the molecular and morphological features of a transformed cell and lead to erroneous interpretation of its cell-of-origin. This review questions the fact that the epigenetic context in which a genetic alteration arises has to be taken into account as a key determinant of STS tumor initiation and progression. Retracing the cancer-initiating cell and its clonal evolution, notably via epigenetic approach, appears as a key lever for understanding the origin of these tumors and improving their clinical management.

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