ABSTRACT
Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.
Subject(s)
Burkitt Lymphoma/metabolism , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Lymphoma, B-Cell/metabolism , Proto-Oncogene Proteins c-myc/metabolism , RNA, Long Noncoding/metabolism , Base Sequence , Binding Sites , Cell Cycle , Cell Line , Cell Line, Tumor , Cell Survival , Chromatin/metabolism , Gene Expression Profiling , Humans , In Situ Hybridization, Fluorescence , Molecular Sequence Data , Neoplasms/metabolism , Promoter Regions, Genetic , RNA, Small Interfering/metabolism , Sequence Homology, Nucleic AcidABSTRACT
Scleromyxedema is a rare disorder of connective tissue with unknown etiology. Its manifestation includes a generalized mucin deposition, which is frequently associated with paraproteinemia. The course of scleromyxedema is progressive and often lethal. As a result of its poorly understood pathogenesis, there is no causative treatment option. The efficacy of cytoreductive agents and autologous stem cell transplantation has been reported, but so far allografting as a treatment option has not yet been documented. Herein, we report on a patient with severe neurologic involvement and refractory course attaining durable remission after receiving an allogeneic hematopoietic cell transplant from an human leukocyte antigen-matched sibling. This case not only illustrates a potential new treatment option for selected patients, but also provides insights into the pathogenesis of this rare disease.
Subject(s)
Hematopoietic Stem Cell Transplantation , Scleromyxedema/therapy , Adult , Allografts , Central Nervous System Diseases/etiology , Central Nervous System Diseases/immunology , Central Nervous System Diseases/therapy , Humans , Male , Paraproteinemias/complications , Paraproteinemias/immunology , Paraproteinemias/therapy , Remission Induction , Scleromyxedema/complications , Scleromyxedema/immunology , Translational Research, BiomedicalABSTRACT
GOAL: The desire for shared decision making arises especially for frequently occurring cases of solid cancer. For hematological cancer conditions, there are no analogous results. This study compares the participation patients' desires concerning medical decisions dealing with their solid and hematological tumors. PATIENTS AND METHODS: The 533 inpatients with solid cancer (age<65: 61.0%; female: 39.6 %) and 177 patients with hematological cancer (inpatient: 62.1%, outpatient: 37.9%; age<65: 63.3%; female: 42.4%) were given a questionnaire after admission to a hospital or medical practice. The dependent variable was patient preference for control in decision making for eight different medical areas of decision. RESULTS: Descriptive results showed that patients with solid cancer had a stronger desire to participate in the decisions in six of a total of eight survey fields (p<0.01). When considering medical and socio-demographic control variables, the multivariate regression shows that the differences between the patient groups remain in all areas (p<0.01). Further predictor variables are educational background and age (p<0.05). No influence resulted from the factors of gender, medical or treatment characteristics. CONCLUSION: The results show differences between patients with hematological cancer and patients with solid tumors, and these differences concern the preference to participate in medical decisions. Hemato-oncological patients desire less active participation and prefer a more dominant role of the physician in the various areas requiring decisions. Physicians should respect this in the course of the treatment.
Subject(s)
Decision Making , Hematologic Neoplasms/therapy , Neoplasms/therapy , Patient Participation , Patient Preference , Physician-Patient Relations , Aged , Female , Hematologic Neoplasms/psychology , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasms/psychology , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
It is becoming more and more common for patients to take an active role when medical decisions have to be made. There are only few results here concerning possibilities and patient preferences for haematological illnesses. This study has interviewed 117 patients with haemato-oncological illnesses at two assessment dates. The desired and the (in the follow up) perceived role in the medical decision-making process were documented. The majority (60.2%) desired more a passive role, which is a considerably higher portion than with solid cancer cases. Roughly every second person interviewed (55.7%) was included - mostly passively - in decisions in accordance with his preferences. The results and limits of the study are also discussed.
Subject(s)
Decision Making , Hematologic Neoplasms/psychology , Patient Participation/psychology , Physician-Patient Relations , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Patient Participation/statistics & numerical dataABSTRACT
Most mesenchymal neoplasms of the gastrointestinal tract belong to the category of gastrointestinal stromal tumors (GISTs) and are characterized by the immunohistochemical expression of KIT receptor. In cases without detectable KIT receptor expression several differential diagnoses have to be taken into consideration. Here, we report a case of a 41-year-old man with a tumor of the small bowel composed of large epithelioid tumor cells arranged in solid and alveolar sheets including scattered osteoclast-like multinucleated giant cells. Immunohistochemically, the tumor cells expressed strongly S-100 protein, vimentin, and to a lesser extent, bcl-2. HMB-45, melan-A, KIT receptor, desmin, smooth-muscle actin, and CD-34 were not detectable. Ki-67 index was 20%. The diagnosis was established by 2 different FISH strategies demostrating the presence of a t(12;22)(q13;q12) translocation, the diagnostic hallmark of clear cell sarcoma of soft parts. Our results provide further evidence for the existence of a new tumor entity designated gastrointestinal clear cell sarcoma with osteoclast-like giant cells. The diagnosis of this entity should be considered in the presence of S-100-positive tumors of the gastrointestinal tract containing multinucleated giant cells and can be established by FISH analysis.
