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Träfflista för sökning "WFRF:(Sundström Johan) ;pers:(Sundström Magnus)"

Sökning: WFRF:(Sundström Johan) > Sundström Magnus

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  • La Fleur, Linnea, et al. (författare)
  • Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
  • 2019
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 130, s. 50-58
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.MATERIALS AND METHODS: Using targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.RESULTS: We obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.CONCLUSION: Here we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.
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  • Birgisson, Helgi, et al. (författare)
  • Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer
  • 2015
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer. Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis. Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination. Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.
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  • Botling, Johan, et al. (författare)
  • Impact of thawing on RNA integrity and gene expression analysis in fresh frozen tissue
  • 2009
  • Ingår i: Diagnostic molecular pathology (Print). - 1052-9551 .- 1533-4066. ; 18:1, s. 44-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Biobanks of fresh, unfixed human tissue represent a valuable source for gene expression analysis in translational research and molecular pathology. The aim of this study was to evaluate the impact of thawing on RNA integrity and gene expression in fresh frozen tissue specimens. Portions of snap frozen tonsil tissue, unfixed or immersed in RNAlater, were thawed at room temperature for 0 minute, 5 minutes, 30 minutes, 45 minutes, 1 hour, 3 hours, 6 hours, and 16 hours before RNA extraction. Additionally, tonsil tissue underwent repetitive freezing and thawing cycles. RNA integrity was analyzed by microchip gel electrophoresis and gene expression by quantitative real-time polymerase chain reaction for selected genes (FOS, TGFB1, HIF1A, BCL2, and PCNA). Minimal RNA degradation was detected after 30 minutes of thawing in unfixed samples. This degradation was accompanied by relevant changes in gene expression for FOS and BCL2 at 45 minutes. Modified primer design or the use of different housekeeping genes could not rectify the changes for FOS. Repetitive thawing cycles had similar effects on RNA integrity. The incubation of the tissue in RNAlater efficiently prevented RNA degradation. In conclusion, degradation of RNA in frozen tissue occurs first after several minutes of thawing. Already minimal decrease in RNA quality may result in significant changes in gene expression patterns in clinical tissue samples.
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  • Bång, Magnus, et al. (författare)
  • Automatisk trafikövervakning genom AI i svenska farvatten : Slutrapport AutoMon Del I
  • 2023
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Denna slutrapport redogör för resultatet av projektet: AutoMon Del I—Automatisk trafikövervakning genom AI i svenska farvatten (TRV2019/95873). Projektägare är Linköpings universitet och genomförts tillsammans med Sjöfartsverket, SAAB, VTI, och Luftfartsverket. Vi kommer i denna rapport redogöra för resultaten samt diskutera framtida utmaningar med konceptet AutoMon. Syftet med AutoMon är att undersöka och belysa problemområdet automatiserad trafikövervakning genom att implementera en AI-demonstrator för svenska farvatten, initialt med fokus på att detektera anomalier i trafiken, och där hanteringen (dvs. granskning och lösning) av problemsituationer lämnas över till en mänsklig operatör. Förekomsten av fartygsolyckor och -incidenter, med potentiellt stora konsekvenser för individ och miljö - utanför etablerade VTS-områden - visar på behovet av utökad övervakning av sjötrafiken i svenska farvatten för att möjliggöra proaktiva åtgärder för att minimera olycksrisker till sjöss. Forskningsprojektet undersöker hur en hög nivå av automation kan användas för att upptäcka och hantera trafikavvikelser på svenskt vatten samt ge möjlighet till s.k. situational awareness (lägesbild) över hela dess yta, samtidigt som stöd för centralt eller distribuerat beslutsfattande ges. Runt om i världen förekommer även manipulation av AIS-systemet och dess positionsangivelser; ett problem som sannolikt kommer att öka även i Sverige. Båda problemställningarna är globala, vilket ger hög relevans. Lösningar har högt värde där digitalisering och artificiell intelligens kan användas som medel för ökad sjösäkerhet (safety och cyber security). 
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  • Edlund, Karolina, et al. (författare)
  • Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database and validation by ultradeep sequencing of human tumors
  • 2012
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:24, s. 9551-9556
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer mutation databases are expected to play central roles in personalized medicine by providing targets for drug development and biomarkers to tailor treatments to each patient. The accuracy of reported mutations is a critical issue that is commonly overlooked, which leads to mutation databases that include a sizable number of spurious mutations, either sequencing errors or passenger mutations. Here we report an analysis of the latest version of the TP53 mutation database, including 34,453 mutations. By using several data-driven methods on multiple independent quality criteria, we obtained a quality score for each report contributing to the database. This score can now be used to filter for high-confidence mutations and reports within the database. Sequencing the entire TP53 gene from various types of cancer using next-generation sequencing with ultradeep coverage validated our approach for curation. In summary, 9.7% of all collected studies, mostly comprising numerous tumors with multiple infrequent TP53 mutations, should be excluded when analyzing TP53 mutations. Thus, by combining statistical and experimental analyses, we provide a curated mutation database for TP53 mutations and a framework for mutation database analysis.
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  • Grundberg, Ida, 1982-, et al. (författare)
  • Diagnostic mutation testing in situ in routine FFPE tissue sections for treatment prediction in clinical oncology
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Activating mutations in the KRAS gene are present in different cancer types and are strongly associated with resistance to epidermal growth factor receptor (EGFR) inhibitor therapy. Hence there is a requirement for sensitive KRAS mutation analysis to determine the most suitable treatment for the patients. Also, little is known about the impact of tumor heterogeneity with regard to KRAS mutation status in different sub-clones during tumorigenesis, and if this is important for treatment response and prognosis. To improve the diagnostic accuracy, we developed an RNA-based genotyping assay that targets KRAS-mutations in codon 12 and 13 in situ on tissue samples by the use of multiple mutation specific padlock probes and rolling-circle amplification. Thus, the distribution of wild-type (green rolling-circle products) and mutated (red rolling-circle products) KRAS alleles can be determined for single cancer cells in different parts of a heterogeneous tumor without the use of microdissection. We demonstrate reliable detection of KRAS point mutations on cytologic tumor imprints as well as on fresh frozen and formalin-fixed paraffin-embedded tissue sections from colorectal and lung cancer. This in situ method offers single cell mutation detection for diagnostics and holds great promise as a tool to investigate the role of oncogenic mutations in complex tumor tissues.
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