| 1. |
- Bergstrand, Sofie, et al.
(författare)
-
Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome
- 2020
-
Ingår i: Cell Death and Disease. - : Nature Publishing Group. - 2041-4889. ; 11:4
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 2. |
- Egelberg, Moa, et al.
(författare)
-
Low levels of WRAP53 predict decreased efficacy of radiotherapy and are prognostic for local recurrence and death from breast cancer : a long-term follow-up of the SweBCG91RT randomized trial
- 2023
-
Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 17:10, s. 2029-2040
-
Tidskriftsartikel (refereegranskat)abstract
- Downregulation of the DNA repair protein WD40-encoding RNA antisense to p53 (WRAP53) has been associated with radiotherapy resistance and reduced cancer survival. The aim of this study was to evaluate WRAP53 protein and RNA levels as prognostic and predictive markers in the SweBCG91RT trial, in which breast cancer patients were randomized for postoperative radiotherapy. Using tissue microarray and microarray-based gene expression, 965 and 759 tumors were assessed for WRAP53 protein and RNA levels, respectively. Correlation with local recurrence and breast cancer-related death was assessed for prognosis, and the interaction between WRAP53 and radiotherapy in relation to local recurrence was assessed for radioresistance prediction. Tumors with low WRAP53 protein levels had a higher subhazard ratio (SHR) for local recurrence [1.76 (95% CI 1.10–2.79)] and breast cancer-related death [1.55 (1.02–2.38)]. Low WRAP53 RNA levels were associated with almost a three-fold decreased effect of radiotherapy in relation to ipsilateral breast tumor recurrence [IBTR; SHR 0.87 (95% CI 0.44–1.72)] compared with high RNA levels [0.33 (0.19–0.55)], with a significant interaction (P = 0.024). In conclusion, low WRAP53 protein is prognostic for local recurrence and breast cancer-related death. Low WRAP53 RNA is a potential marker for radioresistance.
|
|
| 3. |
- Ranhem, Cecilia, et al.
(författare)
-
Evaluation of dyskerin expression and the Cajal body protein WRAP53 beta as potential prognostic markers for patients with primary vaginal carcinoma
- 2022
-
Ingår i: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53 beta), 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 WRAP53 beta in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis 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 WRAP53 beta 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 significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53 beta 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.
|
|
| 4. |
|
|
| 5. |
- Ranhem, Cecilia, et al.
(författare)
-
Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
- 2022
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Primary vaginal cancer (PVC) is a rare gynaecological 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 prognosis 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 significantly 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.
|
|
| 6. |
- Ranhem, Cecilia, et al.
(författare)
-
Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
- 2022
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 7. |
- Renberg, Markus, et al.
(författare)
-
Patient-reported outcome measures and their association to the original Strickland classification after flexor tendon repair
- 2023
-
Ingår i: Journal of Hand Surgery, European Volume. - : SAGE PUBLICATIONS LTD. - 1753-1934 .- 2043-6289. ; 48:7, s. 661-667
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the relationship between patient-reported outcome measures (PROMs) and the original Strickland classification after flexor tendon injuries in Zones 1 and 2. Data were collected from the Swedish national health care registry for hand surgery (HAKIR). The studied PROMs were the Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) and the patient questionnaire from the HAKIR (HQ-8). Complete data of both range of motion (ROM) and PROMs were available for 215 patients at 3 months after surgery, and for 150 patients at 12 months after surgery. We found that QuickDASH values were low and similar between all groups as classified by the Strickland system at 12 months. A statistically significant difference between PROM values (for stiffness and satisfaction) was found only between the Strickland groups Fair and Good, but not between Poor and Fair or Good and Excellent. This suggests that further categorization according to the Strickland classification is less important to the patients as long as they regain 70% of their ROM.
|
|
| 8. |
- Svingen, Jonas, et al.
(författare)
-
Risk factors for reoperation after flexor tendon repair : a registry study
- 2022
-
Ingår i: Journal of Hand Surgery, European Volume. - : SAGE Publications. - 1753-1934 .- 2043-6289. ; 47:10, s. 1071-1076
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
