The eukaryotic genome must be precisely organized for its proper function, as genome topology impacts transcriptional regulation, cell division, replication, and repair, among other essential processes. Disruptions to human genome topology can lead to diseases, including cancer. The advent of chromosome conformation capture with high-throughput sequencing (Hi-C) to assess genome organization has revolutionized the study of nuclear genome topology; Hi-C has elucidated numerous genomic structures, including chromosomal territories, active/silent chromatin compartments, Topologically Associated Domains, and chromatin loops. While low-resolution heatmaps can provide important insights into chromosomal level contacts, high resolution Hi-C datasets are required to reveal folding principles of individual genes. Of particular interest are high-resolution chromosome conformation datasets of organisms modeling the human genome. Here, we report the genome topology of the fungal model organism Neurospora crassa at a high resolution. Our composite Hi-C dataset, which merges two independent datasets generated with restriction enzymes that monitor euchromatin (DpnII) and heterochromatin (MseI), along with our DpnII/MseI double digest dataset, provide exquisite detail for both the conformation of entire chromosomes and the folding of chromatin at the resolution of individual genes. Within constitutive heterochromatin, we observe strong yet stochastic internal contacts, while euchromatin enriched with either activating or repressive histone post-translational modifications associates with constitutive heterochromatic regions, suggesting inter-compartment contacts form to regulate transcription. Consistent with this, a strain with compromised heterochromatin experiences numerous changes in gene expression. Our high-resolution Neurospora Hi-C datasets are outstanding resources to the fungal community and provide valuable insights into higher organism genome topology.

Background: Primary soft tissue or bone METs are very rare neoplasms. Data on prognosis and outcome are sparse.Methods: We retrospectively reviewed the METs managed by the French Sarcoma Group between 1990 and 2019. Glandular and visceral tumors were excluded. Survival curves for operated patients were calculated using the Kaplan-Meier method. Univariate analysis was performed using the logrank test and the Cox proportional hazards model for the identification of prognostic factors (PF).Results: A total of 83 patients were treated in 14 centers. In 7 cases, MET was first misdiagnosed with mimick. Median age was 43 years (3-85). There were 45 women (54%). METs occurred in bone in 4 cases (5%) and in soft tissue in 79 (95%). The most common primary sites were the lower limbs (33, 40%), the upper limbs (23, 28%), and the trunk wall (15, 18%). Median size was 50 mm (7-400). 24 (30%) were superficial tumors. Initial N1 (pathological lymph nodes) and M1 (distant metastasis) status were diagnosed in 4 (5%) and 5 (6%) cases, respectively. 75 patients (90%) underwent curative-intent surgery with 32 (39%) R0 resection, 21 (25%) R1 and 5 (6%) R2. 5 patients (6%) received perioperative chemotherapy, 3 (4%) preoperative radiotherapy, and 18 (22%) adjuvant radiotherapy. Median follow-up was 58 months. The overall survival (OS) rate at 6, 12 and 24 months was 96% [88-99], 93% [85][86][87][88][89][90][91][92][93][94][95][96][97] and 90% [80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95], respectively. Local relapse-free survival at 6, 12 and 24 months was 90% [80-95], 80% [70-88], and 70% [58-79], respectively. Metastasis-free survival at 6, 12 and 24 months was 86% [77-92], 85% [75-91] and 81% [70-88], respectively. Age 50 years was the only PF for OS , p¼.04). We found three PF for local relapse: misdiagnosis before treatment (HR ¼ 3.