AIMS: Spindle-cell/sclerosing rhabdomyosarcomas (SS-RMS) are clinically and genetically heterogeneous. They include three well-defined molecular subtypes, of which those with EWSR1/FUS::TFCP2 rearrangements were described only recently. This study aimed to evaluate five new cases of SS-RMS and to perform a clinicopathological and statistical analysis of all TFCP2-rearranged SS-RMS described in the English literature to more comprehensively characterize this rare tumour type. METHODS AND RESULTS: Cases were retrospectively selected and studied by immunohistochemistry, fluorescence in situ hybridization with EWSR1/FUS and TFCP2 break-apart probes, next-generation sequencing (Archer FusionPlex Sarcoma kit and TruSight RNA Pan-Cancer Panel). The PubMed database was searched for relevant peer-reviewed English reports. Five cases of SS-RMS were found. Three cases were TFCP2 rearranged SS-RMS, having FUSex6::TFCP2ex2 gene fusion in two cases and triple gene fusion EWSR1ex5::TFCP2ex2, VAX2ex2::ALKex2 and VAX2intron2::ALKex2 in one case. Two cases showed rhabdomyoblastic differentiation and spindle-round cell/sclerosing morphology, but were characterized by novel genetic fusions including EWSR1ex8::ZBTB41ex7 and PLOD2ex8::RBM6ex7, respectively. In the statistical analysis of all published cases, CDKN2A or ALK alterations, the use of standard chemotherapy and age at presentation in the range of 18-24 years were negatively correlated to overall survival. CONCLUSION: EWSR1/FUS::TFCP2-rearranged SS-RMS is a rare rhabdomyosarcoma subtype, affecting predominantly young adults with average age at presentation 34 years (median 29.5 years; age range 7-86 years), with a predilection for craniofacial bones, rapid clinical course with frequent bone and lung metastases, and poor prognosis (3-year overall survival rate 28%).
- Klíčová slova
- ALK, CDKN2A/B, EWSR1, FUS, MyoD1, PLOD2, RBM6, TFCP2, ZBTB41, epithelioid, intraosseous, molecular genetics, rhabdomyosarcoma, spindle cell,
- MeSH
- dítě MeSH
- DNA vazebné proteiny genetika MeSH
- dospělí MeSH
- fúze genů MeSH
- hybridizace in situ fluorescenční MeSH
- lidé středního věku MeSH
- lidé MeSH
- lysinhydroxylasa genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery genetika MeSH
- protein EWS vázající RNA genetika MeSH
- proteiny vázající RNA genetika MeSH
- retrospektivní studie MeSH
- rhabdomyosarkom * genetika patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktory * genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- EWSR1 protein, human MeSH Prohlížeč
- lysinhydroxylasa MeSH
- nádorové biomarkery MeSH
- PLOD2 protein, human MeSH Prohlížeč
- protein EWS vázající RNA MeSH
- proteiny vázající RNA MeSH
- RBM6 protein, human MeSH Prohlížeč
- TFCP2 protein, human MeSH Prohlížeč
- transkripční faktory * MeSH
Lysine hydroxylation of type I collagen telopeptides varies from tissue to tissue, and these distinct hydroxylation patterns modulate collagen cross-linking to generate a unique extracellular matrix. Abnormalities in these patterns contribute to pathologies that include osteogenesis imperfecta (OI), fibrosis, and cancer. Telopeptide procollagen modifications are carried out by lysyl hydroxylase 2 (LH2); however, little is known regarding how this enzyme regulates hydroxylation patterns. We identified an ER complex of resident chaperones that includes HSP47, FKBP65, and BiP regulating the activity of LH2. Our findings show that FKBP65 and HSP47 modulate the activity of LH2 to either favor or repress its activity. BiP was also identified as a member of the complex, playing a role in enhancing the formation of the complex. This newly identified ER chaperone complex contributes to our understanding of how LH2 regulates lysyl hydroxylation of type I collagen C-telopeptides to affect the quality of connective tissues. © 2017 American Society for Bone and Mineral Research.
- MeSH
- biologické modely MeSH
- buněčné linie MeSH
- chaperon endoplazmatického retikula BiP MeSH
- hmotnostní spektrometrie MeSH
- hydroxylace MeSH
- kolagen typu I metabolismus MeSH
- lidé MeSH
- lysin metabolismus MeSH
- lysinhydroxylasa metabolismus MeSH
- multiproteinové komplexy metabolismus MeSH
- mutace genetika MeSH
- myši MeSH
- peptidy metabolismus MeSH
- povrchová plasmonová rezonance MeSH
- prokolagen metabolismus MeSH
- proteiny tepelného šoku HSP47 metabolismus MeSH
- proteiny tepelného šoku metabolismus MeSH
- proteiny vázající takrolimus metabolismus MeSH
- stabilita enzymů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chaperon endoplazmatického retikula BiP MeSH
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- FKBP10 protein, human MeSH Prohlížeč
- kolagen typu I MeSH
- lysin MeSH
- lysinhydroxylasa MeSH
- multiproteinové komplexy MeSH
- peptidy MeSH
- prokolagen MeSH
- proteiny tepelného šoku HSP47 MeSH
- proteiny tepelného šoku MeSH
- proteiny vázající takrolimus MeSH
- SERPINH1 protein, human MeSH Prohlížeč
