Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma.

Noradrenergic and mesenchymal identities have been characterized in neuroblastoma cell lines according to their epigenetic landscapes and core regulatory circuitries. However, their relationship and relative contribution in patient tumors remain poorly defined. We now document spontaneous and reversible plasticity between the two identities, associated with epigenetic reprogramming, in several neuroblastoma models. Interestingly, xenografts with cells from each identity eventually harbor a noradrenergic phenotype suggesting that the microenvironment provides a powerful pressure towards this phenotype. Accordingly, such a noradrenergic cell identity is systematically observed in single-cell RNA-seq of 18 tumor biopsies and 15 PDX models. Yet, a subpopulation of these noradrenergic tumor cells presents with mesenchymal features that are shared with plasticity models, indicating that the plasticity described in these models has relevance in neuroblastoma patients. This work therefore emphasizes that intrinsic plasticity properties of neuroblastoma cells are dependent upon external cues of the environment to drive cell identity.

Effectiveness of radiotherapy to prevent recurrence of heterotopic ossification in patients with spinal cord injury and traumatic head injury: A retrospective case-controlled study.

OBJECTIVE: To evaluate recurrence and early postoperative complications (sepsis) following surgical excision combined with radiotherapy for troublesome hip heterotopic ossification in patients with spinal cord injury and traumatic brain injury. DESIGN: Retrospective case-control study. SETTING: Data relating to patients with spinal cord injury or traumatic brain injury who underwent surgical excision of hip heterotopic ossification were retrieved from the BANKHO database. Case patients underwent excision + radiotherapy and controls underwent excision only. Control patients were matched to case patients according to sex and age (± 4 years). PARTICIPANTS: Data from 19 case patients and 76 controls were analysed. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary end-point was recurrence of heterotopic ossification. Secondary end-points were postoperative complications and, more specifically, sepsis that required surgical revision. RESULTS: There was no difference between the odds ratios (OR) for recurrence for each group (OR case group = 0.63, OR spinal cord injury subgroup = 0.45 and OR head injury subgroup = 1.04). The rate of sepsis requiring surgical revision was significantly higher in the case group (p < 0.05). CONCLUSION: Based on the results of this case-control study, we suggest that radiotherapy should not be combined with surgery in patients with troublesome hip heterotopic ossification undergoing excision. Radiotherapy does not appear to prevent recurrence and, moreover, it is associated with an increased risk of postoperative sepsis.