例如:"lncRNA", "apoptosis", "WRKY"

NR4A3 fusion proteins trigger an axon guidance switch that marks the difference between EWSR1 and TAF15 translocated extraskeletal myxoid chondrosarcomas.

J Pathol. 2019 Sep;249(1):90-101. doi:10.1002/path.5284. Epub 2019 May 14
Monica Brenca 1 , Silvia Stacchiotti 2 , Kelly Fassetta 1 , Marta Sbaraglia 3 , Milijana Janjusevic 1 , Dominga Racanelli 1 , Maurizio Polano 1 , Sabrina Rossi 3 , Silvia Brich 4 , Gian P Dagrada 5 , Paola Collini 6 , Chiara Colombo 7 , Alessandro Gronchi 7 , Annalisa Astolfi 8 , Valentina Indio 8 , Maria A Pantaleo 8 , Piero Picci 9 , Paolo G Casali 10 , Angelo P Dei Tos 11 , Silvana Pilotti 6 , Roberta Maestro 1
Monica Brenca 1 , Silvia Stacchiotti 2 , Kelly Fassetta 1 , Marta Sbaraglia 3 , Milijana Janjusevic 1 , Dominga Racanelli 1 , Maurizio Polano 1 , Sabrina Rossi 3 , Silvia Brich 4 , Gian P Dagrada 5 , Paola Collini 6 , Chiara Colombo 7 , Alessandro Gronchi 7 , Annalisa Astolfi 8 , Valentina Indio 8 , Maria A Pantaleo 8 , Piero Picci 9 , Paolo G Casali 10 , Angelo P Dei Tos 11 , Silvana Pilotti 6 , Roberta Maestro 1
+ et al

[No authors listed]

Author information
  • 1 Unit of Oncogenetics and Functional Oncogenomics, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, Italy.
  • 2 Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  • 3 Department of Pathology, Treviso Regional Hospital, Treviso, Italy.
  • 4 Unit of Experimental Molecular Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  • 5 Laboratory of Molecular Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  • 6 Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  • 7 Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  • 8 "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
  • 9 Laboratory of Experimental Oncology, IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy.
  • 10 Oncology and Haemato-Oncology Department, University of Milan, Milano, Italy.
  • 11 Department of Medicine, University of Padua School of Medicine, Padova, Italy.

摘要


Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma histotype with uncertain differentiation. EMC is hallmarked by the rearrangement of the NR4A3 gene, which in most cases fuses with EWSR1 or TAF15. TAF15-translocated EMC seem to feature a more aggressive course compared to EWSR1-positive EMCs, but whether the type of NR4A3 chimera impinges upon EMC biology is still largely undefined. To gain insights on this issue, a series of EMC samples (7 EWSR1-NR4A3 and 5 TAF15-NR4A3) were transcriptionally profiled. Our study unveiled that the two EMC variants display a distinct transcriptional profile and that the axon guidance pathway is a major discriminant. In particular, class 4-6 semaphorins and axonal guidance cues endowed with pro-tumorigenic activity were more expressed in TAF15-NR4A3 tumors; vice versa, class 3 semaphorins, considered to convey growth inhibitory signals, were more abundant in EWSR1-NR4A3 EMC. Intriguingly, the dichotomy in axon guidance signaling observed in the two tumor variants was recapitulated in in vitro cell models engineered to ectopically express EWSR1-NR4A3 or TAF15-NR4A3. Moreover, TAF15-NR4A3 cells displayed a more pronounced tumorigenic potential, as assessed by anchorage-independent growth. Overall, our results indicate that the type of NR4A3 chimera dictates an axon guidance switch and impacts on tumor cell biology. These findings may provide a framework for interpretation of the different clinical-pathological features of the two EMC variants and lay down the bases for the development of novel patient stratification criteria and therapeutic approaches. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

KEYWORDS: EWSR1, NR4A3, TAF15, axon guidance, extraskeletal myxoid chondrosarcomas, sarcoma, transcriptional profile