EWSR1-SMAD3fibroblastic tumour of bone: expanding the clinical spectrum
SKELETAL RADIOLOGY
Authors: De Noon, Solange; Flanagan, Adrienne M.; Tirabosco, Roberto; O'Donnell, Paul; Amary, Fernanda
Abstract
EWSR1-SMAD3fibroblastic tumour is a recently described soft tissue lesion. To date, eight cases have been reported, all sited in superficial soft tissue, typically occurring in the hands and feet with a tendency for local recurrence if incompletely excised. No metastatic spread has been reported, and hence, these tumours are currently considered benign. Herein, we present the radiological and histological features of the first reported occurrence of this entity in bone: a 44-year-old man with a tumour in the right tibia, treated with en bloc resection and showing no signs of relapse at 7 years. This tumour should be added to the differential diagnosis of bone lesions which harbourEWSR1gene rearrangement.
The testis protein ZNF165 is a SMAD3 cofactor that coordinates oncogenic TGF beta signaling in triple-negative breast cancer
ELIFE
Authors: Gibbs, Zane A.; Reza, Luis C.; Cheng, Chun-Chun; Westcott, Jill M.; McGlynn, Kathleen; Whitehurst, Angelique W.
Abstract
Cancer/testis (CT) antigens are proteins whose expression is normally restricted to germ cells yet aberrantly activated in tumors, where their functions remain relatively cryptic. Here we report that ZNF165, a CT antigen frequently expressed in triple-negative breast cancer (TNBC), associates with SMAD3 to modulate transcription of transforming growth factor beta (TGF beta)-dependent genes and thereby promote growth and survival of human TNBC cells. In addition, we identify the KRAB zinc finger protein, ZNF446, and its associated tripartite motif protein, TRIM27, as obligate components of the ZNF165-SMAD3 complex that also support tumor cell viability. Importantly, we find that TRIM27 alone is necessary for ZNF165 transcriptional activity and is required for TNBC tumor growth in vivo using an orthotopic xenograft model in immunocompromised mice. Our findings indicate that aberrant expression of a testis-specific transcription factor is sufficient to co-opt somatic transcriptional machinery to drive a protumorigenic gene expression program in TNBC.