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Human cancer genome sequencing has recently revealed that genes encoding subunits of SWI/SNF chromatin remodeling complexes are frequently mutated across a wide variety of cancers, and several subunits of the complex have been shown to have bona fide tumor suppressor activity1. However, whether mutations in SWI/SNF subunits result in shared dependencies is unknown. Here we show that EZH2, a catalytic subunit of the Polycomb repressive complex 2 (PRC2), is essential in all tested cancer cell lines and xenografts harboring mutations of the SWI/SNF subunits ARID1A, PBRM1, and SMARCA4, which are several of the most frequently mutated SWI/SNF subunits in human cancer but that co–occurrence of a Ras pathway mutation correlates with abrogation of this dependence. Surprisingly, we demonstrate that SWI/SNF mutant cancer cells are primarily dependent upon a non–catalytic role of EZH2 in stabilization of the PRC2 complex, and only partially dependent on EZH2 histone methyltransferase activity. These results not only reveal a shared dependency of cancers with genetic alterations in SWI/SNF subunits, but also suggest that EZH2 enzymatic inhibitors now in clinical development may not fully suppress the oncogenic activity of EZH2.

Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and cell fate are poorly understood. Utilizing mouse embryonic fibroblast and cancer cell line models, here we show via ChIP-seq and biochemical assays that SWI/SNF complexes are preferentially targeted to distal lineage specific enhancers and interact with p300 to modulate histone H3 lysine 27 acetylation. We identify a greater requirement for SWI/SNF at typical enhancers than at most super-enhancers and at enhancers in untranscribed regions than in transcribed regions. Our data further demonstrate that SWI/SNF-dependent distal enhancers are essential for controlling expression of genes linked to developmental processes. Our findings thus establish SWI/SNF complexes as regulators of the enhancer landscape and provide insight into the roles of SWI/SNF in cellular fate control.

SMARCB1 (INI1/SNF5/BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in the large majority of rhabdoid tumors and germline heterozygous SMARCB1 mutations form the basis for rhabdoid predisposition syndrome. Mouse models validated Smarcb1 as a bona fide tumor suppressor as Smarcb1 inactivation in mice results in 100% of the animals rapidly developing cancer. SMARCB1 was the first subunit of the SWI/SNF complex found mutated in cancer. More recently, at least seven other genes encoding SWI/SNF subunits have been identified as recurrently mutated in cancer. Collectively, 20% of all human cancers contain a SWI/SNF mutation. Consequently, investigation of the mechanisms by which SMARCB1 mutation causes cancer has relevance not only for rhabdoid tumors, but also potentially for the wide variety of SWI/NSNF mutant cancers. Here we discuss normal functions of SMARCB1 and the SWI/SNF complex as well as mechanistic and potentially therapeutic insights that have emerged.

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The purpose of this study was to identify the clinical experiences of nursing students that were anxiety provoking and examine the relationship between the level of trait anxiety and the clinical experience that produced anxiety in nursing students. A descriptive correlational design collected data from 61 nursing students in their last semester of the baccalaureate nursing program using survey questionnaires that captured demographic data and included the Trait Anxiety Scale and the Clinical Experience Assessment form. Analyses of data indicate that 36% of the students experienced a moderate level of anxiety. Clinical experiences related to arriving late, being observed by instructors, responding to initial experiences, having a fear of making mistakes, and talking to physicians were the most anxiety producing for these students. A significantly positive relationship (r = .40, p < .05) was found between the trait anxiety and clinical experience that was anxiety producing. A higher level of perceived anxiety accompanied the following clinical experiences; being observed by instructors (F = 3.44, p = .04), doing beforehand in-hospital preparation (F = 4.46, p < .02), asking questions of faculty (F = 4.38, p < .02), being evaluated by faculty (F = 3.37, p < .04), and reporting to team leader (F = 3.60, p < .05). The most anxiety producing clinical experiences in nursing students before graduation are evaluated with descriptive data. Results would provide useful insights for faculty and senior nursing students involved in clinical practice, and have implications for education, further research, and clinical support.

Clinical preceptorship provides an essential aspect of nursing education for senior nursing students. This descriptive study identified perceptions of senior nursing students about their clinical preceptorship experiences, evaluated their perceived levels of competency and confidence in providing nursing care; and examined their perceived confidence level in relation to the perceived competency level of nursing skills. Researchers approached 134 culturally diverse senior nursing students enrolled in Preceptorship courses at one of the state-funded California universities and collected anonymous data from 95 students in academic years 2010-2012, using three instruments; Senior Preceptorship Experience Questionnaire, Graduate Nurse Survey, and Quality and Safety Education for Nurses tools. Results indicated that the clinical preceptorship improved students' perceived competency skills and confidence in providing nursing care. Outcomes demonstrated that the level of students' perceived competency was positively associated with the level of their interaction with preceptor. There was a significant correlation between the overall perceived competency level and confidence level of students; however there was no relationship between the amount of preceptor interaction and the degree of perceived confidence. This information is useful to nursing education as educators continue striving to reconcile the lack of preparedness for new staff roles that employers see in new graduates. International Journal of Nursing, Vol. 1(2), December 2014 Keywords IntroductionA senior preceptorship embraces culmination of students' roles as nursing students; and it helps students attain the very beginning of their nursing career as professional nurses. During this time, student nurses transition into functional independent nurses under the supervision of a preceptor that serves as a clinical expert, role model, and direct supervisor of the preceptee. The students, known as preceptees, are expected to increase their workload gradually, until they are able to take on the full patient assignment. Benefits from this experience may include building professional roles, competence, confidence, and socialization in the nursing practice; as well as developing and achieving personal goals, learning about accountability, and becoming more familiarized with the organizational culture. The sum of these skills allows preceptees to deliver quality care to their patients.Literature indicates that the transition from a student nurse to novice staff nurse could be a stressful experience. Student nurses felt frustrated when they did not receive adequate support during transition (Kumaran & Carney, 2014) and experienced significantly more stress during their academic preparation, especially during their senior clinical preceptorship than they did during the first year of employment (Younge, Myrick, & Haase, 2002). The change in role might increase unpleasant feelings such as frustration, anxiety, and depressed mood. These negative feelings (Mamchur &...

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