Key Points• Hundreds of lineage-specific lncRNAs are expressed during mouse and human erythropoiesis.• Most mouse erythroid lncRNAs are not expressed in human erythroblasts and vice versa, yet some appear to be functional.Mammals express thousands of long noncoding (lnc) RNAs, a few of which are known to function in tissue development. However, the entire repertoire of lncRNAs in most tissues and species is not defined. Indeed, most lncRNAs are not conserved, raising questions about function. We used RNA sequencing to identify 1109 polyadenylated lncRNAs expressed in erythroblasts, megakaryocytes, and megakaryocyte-erythroid precursors of mice, and 594 in erythroblasts of humans. More than half of these lncRNAs were unannotated, emphasizing the opportunity for new discovery through studies of specialized cell types. Analysis of the mouse erythro-megakaryocytic polyadenylated lncRNA transcriptome indicates that ∼75% arise from promoters and 25% from enhancers, many of which are regulated by key transcription factors including GATA1 and TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatic speciesspecificity. RNA interference assays of 21 abundant erythroid-specific murine lncRNAs in primary mouse erythroid precursors identified 7 whose knockdown inhibited terminal erythroid maturation. At least 6 of these 7 functional lncRNAs have no detectable expression in human erythroblasts, suggesting that lack of conservation between mammalian species does not predict lack of
Based on this large review of patients with sinonasal mucosal melanoma, adjuvant radiation therapy may not provide a survival benefit as patients tended to do poorly regardless of adjuvant radiation status.
Background Given the rarity of esthesioneuroblastoma, it is difficult to validate a staging system. The purpose of this study was to investigate the utility of the Kadish staging system in esthesioneuroblastoma using the National Cancer Database (NCDB). Methods One thousand one hundred sixty-seven patients with esthesioneuroblastoma were identified from the NCDB. Results Five-year survival was 80.0% for Kadish A, 87.7% for Kadish B, 77.0% for Kadish C, and 49.5% for Kadish D. Kadish B had higher survival than Kadish A. More Kadish B patients received surgery with adjuvant therapy than Kadish A patients (41.6% vs 32.5%; P = .0038) and also had more positive margins (21.6% vs 11.3%; P = .03). There was no difference in age distribution, sex, race, or neck dissection status between the 2 groups. Conclusion Kadish B had greater survival than Kadish A, but the treatment characteristics could not account for this difference. The utility of early-stage Kadish staging is uncertain and requires further study.
Objective To describe patient demographics, histology, treatment modalities, and survival associated with adult sinonasal rhabdomyosarcoma. Study Design Retrospective review of a national database. Setting Tertiary medical center. Subjects and Methods Patient demographics, tumor histology, treatment modalities, and survival trends were examined for patients aged ≥18 years who were diagnosed with sinonasal rhabdomyosarcoma between 2004 and 2013 with the National Cancer Database. Kaplan-Meier analysis and the log-rank tests were performed to determine the unadjusted association between overall survival and various patient and disease characteristics. Results A total of 186 patients were identified; 5-year overall survival was 28.4%. Over half of patients were between 18 and 35 years old at diagnosis (53.8%), which was associated with improved 5-year overall survival over patients >35 years old (31.9% vs 24.4%, P = .014). Alveolar sinonasal rhabdomyosarcoma was most common (66.7%). There was no statistical difference in 5-year overall survival between alveolar and embryonal subtypes (30.5% vs 41.6%, P > .05). Metastatic disease was present in 27.7% of patients and was associated with worse 5-year overall survival (14.7% vs 33.9%, P < .0001). The majority of patients were treated with chemotherapy with adjuvant radiation (49.5%). A quarter of patients were treated with surgery plus chemoradiation (25.8%). Conclusion We present the largest analysis of adult sinonasal rhabdomyosarcoma using a standardized national based database. Adult sinonasal rhabdomyosarcoma has a very poor prognosis independent of histologic subtype. The small number of surgical cases limits the ability of the analysis to accurately compare treatment with chemoradiation with and without surgery.
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