BACKGROUND: @entity703 ( @entity703 ) is a rare and highly aggressive @entity5 that most often occurs in the setting of sickle cell trait or @entity3458 ( @entity3458 ). Most @entity1 present with @entity3 resistant to conventional chemotherapy, and therefore there is an urgent need for molecular insight to propose new therapies. OBJECTIVE: To determine the molecular alterations and oncogenic pathways that drive @entity703 development. DESIGN, SETTING, AND @entity1 : A series of five frozen samples of @entity1 with @entity703 was investigated by means of gene expression profiling, array comparative genomic hybridization, and RNA and whole exome sequencing (WES). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA and DNA sequencing read data were analyzed to detect gene fusions and somatic mutations. Gene fusions mutations were validated by real-time polymerase chain reaction and fluorescence in situ hybridization. Gene expression profiling was analyzed by unsupervised hierarchical clustering and Gene Set Enrichment Analysis (Broad Institute, Cambridge, MA, USA). RESULTS AND LIMITATIONS: We observed inactivation of the @entity5 suppressor gene @entity6195 in all @entity5 . In all four cases developed in @entity1 with @entity3458 , we identified an original mechanism of interchromosomal balanced translocations that disrupt the @entity6195 sequence and thus contribute to its inactivation. Gene expression profiling revealed that @entity703 shares common oncogenic pathways with pediatric @entity5606 , another @entity5 subtype characterized by @entity6195 deficiency. CONCLUSIONS: RMCs are characterized by an original mechanism of interchromosomal balanced translocations that disrupt the @entity6195 sequence. WES reveals that RMCs show no other recurrent @entity74 and an overall stable genome, underscoring the oncogenic potency of @entity6195 inactivation. @entity1 SUMMARY: Our comprehensive molecular study supports a pivotal role of the @entity5 suppressor gene @entity6195 in the development of @entity703 . The use of therapeutic strategies based on the biologic effects of its inactivation should now open new perspectives for this typically lethal @entity5 .

Balanced Translocations Disrupting XXXX Are Hallmark Recurrent Genetic Alterations in @entity703 .

@entity1 :: ('9606', 'Species') :: ['patients', 'PARTICIPANTS', 'PATIENT'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'malignancy', 'neoplasm'] @entity3458 :: ('MESH:D000755', 'Disease') :: ['SCD', 'sickle cell disease'] @entity5606 :: ('MESH:D018335', 'Disease') :: ['malignant rhabdoid tumors'] @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic alteration'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic disease'] @entity6195 :: ('6598', 'Gene') :: ['SMARCB1'] @entity703 :: ('MESH:D007680', 'Disease') :: ['renal medullary carcinoma', 'Renal medullary carcinoma', 'RMC']
@entity6195 :: (6598,Gene) :: ['SMARCB1']
