WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies

The WRAP53 protein regulates the formation and maintenance of Cajal bodies (nuclear sub-organelles), as well as directs the recruitment of nuclear factors to Cajal bodies

Risk factors for reoperation after flexor tendon repair : a registry study

The aim of this study was to identify risk factors for reoperations after Zones 1 and 2 flexor tendon repairs. A multiple logistic regression model was used to identify risk factors from data collected via the Swedish national health care registry for hand surgery (HAKIR). The studied potential risk factors were age and gender, socio-economics and surgical techniques. Included were 1372 patients with injuries to 1585 fingers and follow-up of at least 12 months (median 37 IQR 27-56). Tendon ruptures occurred in 80 fingers and tenolysis was required in 76 fingers. Variables that affected the risk of rupture were age >25 years (p < 0.001), flexor pollicis longus tendon injuries (p < 0.001) and being male (p = 0.004). Injury to both finger flexors had an effect on both rupture (p = 0.005) and tenolysis (p < 0.001). Understanding the risk factors may provide important guidance both to surgeons and therapists when treating patients with flexor tendon injuries

Risk factors for reoperation after flexor tendon repair : a registry study

The aim of this study was to identify risk factors for reoperations after Zones 1 and 2 flexor tendon repairs. A multiple logistic regression model was used to identify risk factors from data collected via the Swedish national health care registry for hand surgery (HAKIR). The studied potential risk factors were age and gender, socio-economics and surgical techniques. Included were 1372 patients with injuries to 1585 fingers and follow-up of at least 12 months (median 37 IQR 27-56). Tendon ruptures occurred in 80 fingers and tenolysis was required in 76 fingers. Variables that affected the risk of rupture were age &gt;25 years (p &lt; 0.001), flexor pollicis longus tendon injuries (p &lt; 0.001) and being male (p = 0.004). Injury to both finger flexors had an effect on both rupture (p = 0.005) and tenolysis (p &lt; 0.001). Understanding the risk factors may provide important guidance both to surgeons and therapists when treating patients with flexor tendon injuries.Funding Agencies|AFA insurance in Sweden [170246]</p

Risk factors for reoperation after flexor tendon repair : a registry study

The aim of this study was to identify risk factors for reoperations after Zones 1 and 2 flexor tendon repairs. A multiple logistic regression model was used to identify risk factors from data collected via the Swedish national health care registry for hand surgery (HAKIR). The studied potential risk factors were age and gender, socio-economics and surgical techniques. Included were 1372 patients with injuries to 1585 fingers and follow-up of at least 12 months (median 37 IQR 27-56). Tendon ruptures occurred in 80 fingers and tenolysis was required in 76 fingers. Variables that affected the risk of rupture were age &gt;25 years (p &lt; 0.001), flexor pollicis longus tendon injuries (p &lt; 0.001) and being male (p = 0.004). Injury to both finger flexors had an effect on both rupture (p = 0.005) and tenolysis (p &lt; 0.001). Understanding the risk factors may provide important guidance both to surgeons and therapists when treating patients with flexor tendon injuries.Funding Agencies|AFA insurance in Sweden [170246]</p

WRAP53 beta, survivin and p16(INK4a) expression as potential predictors of radiotherapy/chemoradiotherapy response in T2N0-T3N0 glottic laryngeal cancer

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53 beta, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linkping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53 beta revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53 beta as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.Funding Agencies|Swedish Cancer Society [2010/545]; County Council of Ostergotland; Research Funds of Linkoping University Hospital; Finnish Cancer Society; Finnish Medical Foundation; Finnish-Norwegian Medical Foundation; Helsinki University Hospital Research Funds [TYH2015204]</p

Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome

Approximately half of all cases of Hoyeraal-Hreidarsson syndrome (HHS), a multisystem disorder characterized by bone marrow failure, developmental defects and very short telomeres, are caused by germline mutations in genes related to telomere biology. However, the varying symptoms and severity of the disease indicate that additional mechanisms are involved. Here, a 3-year-old boy with HHS was found to carry biallelic germline mutations in WRAP53 (WD40 encoding RNA antisense to p53), that altered two highly conserved amino acids (L283F and R398W) in the WD40 scaffold domain of the protein encoded. WRAP53 beta (also known as TCAB1 or WDR79) is involved in intracellular trafficking of telomerase, Cajal body functions and DNA repair. We found that both mutations cause destabilization, mislocalization and faulty interactions of WRAP53 beta, defects linked to misfolding by the TRiC chaperonin complex. Consequently, WRAP53 beta HHS mutants cannot elongate telomeres, maintain Cajal bodies or repair DNA double-strand breaks. These findings provide a molecular explanation for the pathogenesis underlying WRAP53 beta-associated HHS and highlight the potential contribution of DNA damage and/or defects in Cajal bodies to the early onset and/or severity of this disease

Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma

Primary vaginal cancer (PVC) is a rare gynae- cological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prog- nosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was signifi- cantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC