| 1. |
- Bausch, Birke, et al.
(author)
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Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention
- 2017
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In: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:9, s. 1204-1212
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Journal article (peer-reviewed)abstract
- IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
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| 2. |
- Bergman, Annika, et al.
(author)
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Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer
- 2009
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In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Taylor & Francis. - 0284-4311 .- 1651-2073. ; 43:5, s. 251-255
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Journal article (peer-reviewed)abstract
- Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.
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| 3. |
- Carlsson, Fredrik, 1968, et al.
(author)
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Do You Enjoy Having More Than Others? Survey Evidence of Positional Goods
- 2003
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Reports (other academic/artistic)abstract
- Although conventional economic theory proposes that only the absolute levels of income and consumption matter for people´s utility, there is much evidence that relative concerns are often important. This paper uses a survey-experimental method to measure people´s perceptions of the degree to which such concerns matter, i.e. the degree of positionality. Based on a representative sample in Sweden, income and cars are found to be highly positional, on average. This is in contrast to leisure and car safety, which may even be completely non-positional.
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| 4. |
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| 5. |
- Carlsson, Fredrik, 1968, et al.
(author)
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Is Transport Safety More Valuable in the Air?
- 2002
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Reports (other academic/artistic)abstract
- Using a contingent valuation survey, people?s willingness to pay for a given risk reduction is found to be much larger when traveling by air compared to by taxi. Follow-up questions revealed that an important reason for this discrepancy is that many experience a higher mental suffering from flying, and that they are willing to pay to reduce this suffering. It was also consistently found that people are willing to pay more for a certain risk reduction if the original price was higher. Policy implications are discussed.
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| 6. |
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| 7. |
- Christofer Juhlin, C., et al.
(author)
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Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene
- 2015
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In: Genes, Chromosomes and Cancer. - : Wiley: 12 months. - 1045-2257 .- 1098-2264. ; 54:9, s. 542-554
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Journal article (peer-reviewed)abstract
- As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. (c) 2015 The Authors. Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc.
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| 8. |
- de Ståhl, Teresita Diaz, et al.
(author)
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The Swedish childhood tumor biobank : systematic collection and molecular characterization of all pediatric CNS and other solid tumors in Sweden
- 2023
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In: Journal of Translational Medicine. - : BioMed Central (BMC). - 1479-5876. ; 21
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Journal article (peer-reviewed)abstract
- The Swedish Childhood Tumor Biobank (BTB) is a nonprofit national infrastructure for collecting tissue samples and genomic data from pediatric patients diagnosed with central nervous system (CNS) and other solid tumors. The BTB is built on a multidisciplinary network established to provide the scientific community with standardized biospecimens and genomic data, thereby improving knowledge of the biology, treatment and outcome of childhood tumors. As of 2022, over 1100 fresh-frozen tumor samples are available for researchers. We present the workflow of the BTB from sample collection and processing to the generation of genomic data and services offered. To determine the research and clinical utility of the data, we performed bioinformatics analyses on next-generation sequencing (NGS) data obtained from a subset of 82 brain tumors and patient blood-derived DNA combined with methylation profiling to enhance the diagnostic accuracy and identified germline and somatic alterations with potential biological or clinical significance. The BTB procedures for collection, processing, sequencing, and bioinformatics deliver high-quality data. We observed that the findings could impact patient management by confirming or clarifying the diagnosis in 79 of the 82 tumors and detecting known or likely driver mutations in 68 of 79 patients. In addition to revealing known mutations in a broad spectrum of genes implicated in pediatric cancer, we discovered numerous alterations that may represent novel driver events and specific tumor entities. In summary, these examples reveal the power of NGS to identify a wide number of actionable gene alterations. Making the power of NGS available in healthcare is a challenging task requiring the integration of the work of clinical specialists and cancer biologists; this approach requires a dedicated infrastructure, as exemplified here by the BTB.
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| 9. |
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Effekter av undervattensljud från havsbaserade vindkraftverk på fisk från Bottniska viken
- 2009
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Reports (other academic/artistic)abstract
- Då efterfrågan på förnyelsebara energikällor är stor kommer det att ske en storskalig utbyggnad av svensk vindkraft. Vindkraftverken anläggs i stora grupper och bildar så kallade vindkraftsparker. Då vindkraftverk till havs har en större produktionskapacitet än liknande på land samt att de ger upphov till färre intressekonflikter kommer utbyggnad ske främst i de svenska kustvattnen (Wenblad & Westerberg, 2007; Öhman & Wilhelmsson, 2005). Det är främst utsjöbankar som är intressanta, då dessa områden faller innanför uppsatta kriterier för vindkraft till havs. Ett av kriterierna är att bottendjupet inte får överstiga 30 meter (Energimyndigheten, 2007). Utsjöbankar är känsliga områden då de inhyser en stor marin artrikedom. Havsbaserade vindkraftsparker kräver därför stor kunskap om miljöeffekter på värdefulla naturområden, potentiella konsekvenser för yrkesfisket samt hur ljudet från vindkraftverken påverkar det marina livet (Wahlberg & Westerberg, 2005; Wenblad & Westerberg, 2007; Öhman & Wilhelmsson, 2005). I denna studie undersökte vi om lågfrekvent undervattensljud (6, 15, 30, 60 och 180 Hz), liknande det som genereras av havsbaserade vindkraftverk, ger upphov till beteendeförändringar, förändrat födointag eller ökad nivå av stresshormonet kortisol i blodet hos tre för Bottenviken vanligt förekommande fiskarter; abborre (Perca fluviatilis), mört (Rutilus rutilus) och öring (Salmo trutta).
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| 10. |
- Eriksson, Leif, et al.
(author)
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Skattehandboken
- 2016
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In: Skattehandboken. - Stockholm : Wolters Kluwer Sverige AB.
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Book (other academic/artistic)abstract
- Skattehandboken är en komplett handbok för företagsbeskattning, personbeskattning och moms som fyra gånger om året uppdateras med aktuella bestämmelser. Skattehandboken vänder sig till alla som arbetar med skattefrågor. Det är ett självklart hjälpmedel för varje skattekonsult, ekonomiavdelning, revisor eller redovisningskonsult. De två handbokspärmarna behandlar företagets inkomstbeskattning, d.v.s frågor som rör beräkningen av ett företags skattepliktiga inkomst. Innehållet har disponerats så att det knyter an till företagets resultaträkning, men här behandlas också frågor som dels rör den personliga beskattningen, dels företagets hantering av sociala avgifter, skatteuppbörd m.m. Momsområdet ägnas stort utrymme, liksom internationella skattefrågor.
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