Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional and genomic features of a series of 14 cases.Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n=10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina) or anchored multiplex PCR based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient's age ranged between 11 to 86 years, including 5 pediatric cases. Tumors were located in bone (n=12/14) and soft tissue (n=2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n=8/12). Median survival was 8 months and 5 patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but 3 cases without underlying ALK fusion on break-apart FISH (n=5) nor next generation sequencing (n=14).TFCP2 was fused in 5' either to EWSR1 (n=6) or FUS (n=8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n=8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 12.8 to 90 and CDKN2A deletion was recurrent (n=9/10). FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups.Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas which are associated with a predilection for the craniofacial bones, an aggressive course and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.
Clinical Relevance Enamel microabrasion is an effective first-line esthetic treatment for the removal of tooth stains due to fluorosis, with an improvement in the appearance of teeth that is associated with a high level of patient acceptance.
A BSTRACT Objectives: The dental pulp contains undifferentiated mesenchymal cells, blood vessels and so on, which are responsible for routine functions of a tooth. The determination of stemness and regenerative properties using biomarkers and further application in routine practice may unravel its potential. Materials and Methods: Inclusion criteria— original research articles published in English, from 2000 to 2019, were collected both manually and by electronic search from databases of Cochrane, Medline, Embase, and PubMed. Exclusion criteria— articles other than English and review manuscripts were omitted. The shortlisted articles were reviewed for specific biomarkers, to assess the regenerative potential, stemness, and lineage of dental pulp stem cells. Results: Of 512 articles, 64 were selected and reviewed to determine the mesenchymal, neurogenic, vasculogenic, hematopoietic, and stem cell potential. On the basis of the search analysis, a panel of markers was proposed. Conclusion: The application of proposed markers, on a pulpectomized tissue derived from human teeth, may be helpful to determine the regenerative potential and the usefulness in regenerative medicine and tissue engineering.
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