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- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Davidsson, Josef, et al.
(författare)
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dup(19)(q12q13.2): Array-based Genotype-Phenotype Correlation of a New Possibly Obesity-related Syndrome.
- 2010
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Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 18, s. 580-587
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Tidskriftsartikel (refereegranskat)abstract
- Small supernumerary marker chromosomes (sSMCs) derived from the near-centromeric area of chromosome 2 are very rare. In addition, duplications of the 2p11.2-->q11.2 region have displayed considerable variability between patients harboring and lacking clinical findings. Moreover, constitutional duplication of the 19q12-->q13.2 region has previously only been described in two cases and was associated with delay of developmental milestones, corpus callosum anomalies, and obesity. Herein, we present a genotype-phenotype correlation in a patient harboring two sSMCs derived from chromosomes 2 and 14 or 22, respectively. The DNA was studied using G-banding, fluorescence in situ hybridization techniques, and array-based comparative genomic hybridization. A 48,XX,+der(2)del(2)(p11)del(2)(q11.2),+der(14)t(14;19)(q11;q12)del(19)(q13.31) or 48,XX,+der(2)del(2)(p11)del(2)(q11.2),+der(22)t(22;19)(q11;q12)del(19)(q13.31) was detected in the patient. The sSMC 14;19 or 22;19, with its centromere originating from either chromosome 14 or 22, encompassed a 13.56 megabase (Mb) 19q derived region, harboring 263 genes, and the sSMC 2 a 2.71 Mb region including 29 genes. The patient had symptoms including a ventral septal defect, bilateral grade IV urinary reflux, corpus callosum agenesis, microphthalmia, and obesity. The 19q segment contained the genes AKT2, CEACAM1, CEBPA, LIPE, and TGFB1 which are involved in adipose tissue homeostasis and insulin resistance, and could potentially contribute to the obese phenotype observed. Array-based genetic characterization and long-term clinical evaluation with attention toward weight gain in patients with chromosome 19q duplications might in the future lead to the description of a obesity-associated genetic syndrome, something that could have implications in management and treatment of patients carrying a dup(19)(q12q13.2). Whether the der(2)(p11q11.2) contributes to the phenotype remains inconclusive.
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| 4. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The Value of the UroVysion((R)) Assay for Surveillance of Non-Muscle-Invasive Bladder Cancer.
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 54:2, s. 402-408
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion((R)) (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.
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| 7. |
- Lombardi, Maria Paola, et al.
(författare)
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Mutation update for the PORCN gene
- 2011
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Ingår i: Human Mutation. - : Wiley-Blackwell. - 1059-7794 .- 1098-1004. ; 32:7, s. 723-728
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the PORCN gene were first identified in Goltz-Gorlin syndrome patients in 2007. Since then, several reports have been published describing a large variety of genetic defects resulting in the Goltz-Gorlin syndrome, and mutations or deletions were also reported in angioma serpiginosum, the pentalogy of Cantrell and Limb-Body Wall Complex. Here we present a review of the published mutations in the PORCN gene to date and report on seven new mutations together with the corresponding clinical data. Based on the review we have created a Web-based locus-specific database that lists all identified variants and allows the inclusion of future reports. The database is based on the Leiden Open (source) Variation Database (LOVD) software, and is accessible online at http://www.lovd.nl/porcn. At present, the database contains 106 variants, representing 68 different mutations, scattered along the whole coding sequence of the PORCN gene, and 12 large gene rearrangements, which brings up to 80 the number of unique mutations identified in Goltz-Gorlin syndrome patients.
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| 10. |
- Schlögel, Matthieu J, et al.
(författare)
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No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome.
- 2015
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome (MCLMR) is a rare autosomal dominant disorder with variable expressivity. It is characterized by mild-to-severe microcephaly, often associated with intellectual disability, ocular defects and lymphedema. It can be sporadic or inherited. Eighty-seven patients have been described to carry a mutation in KIF11, which encodes a homotetrameric motor kinesin, EG5.
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