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| 2. |
- Blad, Karin, 1982-, et al.
(författare)
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Sweden
- 2018
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Ingår i: Corporate Tax Residence and Mobility. - Amsterdam, Netherlands : International Bureau of Fiscal Documentation (IBFD). - 9789087224516 - 9789087224400 ; , s. 573-590
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Bokkapitel (refereegranskat)
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| 3. |
- Chen, Yilun, et al.
(författare)
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Identification and use of personalized genomic markers for monitoring circulating tumor DNA
- 2018
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Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1064-3745. ; 1768, s. 303-322
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Bokkapitel (refereegranskat)abstract
- Digital PCR techniques are ideally suited for accurately quantifying trace amounts of target DNA sequences, such as tumor-derived mutant DNA that is present in the blood circulation of patients with cancer. Here, we describe an approach marrying low-coverage whole-genome sequencing of tumor tissues, to enumerate chromosomal rearrangement breakpoints, together with droplet digital PCR (ddPCR)-based personalized rearrangement assays to cost-effectively monitor circulating tumor DNA levels at multiple time-points during the clinical course. The method is generally applicable to essentially any cancer patient, as all cancers harbor unstable genomes, and may have uses for measuring minimal residual disease, response to therapy, and early detection of metastasis.
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| 6. |
- Kulin Olsson, Karin, 1951-
(författare)
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Arvsrätt eller rätt till arv : en studie om arvsberättigande och kvarlåtenskapens fördelning
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present Swedish law of inheritance has developed slowly and is based on ideas stemming from an earlier social structure than that of today. When reforms have been made, modern regulations have been added to a very old structure. The rules on inheritance are still based on the nuclear family, though changes in society and the family forms that people choose have impacted on the notion of family, a notion which can no longer be seen as homogenous and clear. With changing living conditions and new forms of family, the present regulation has resulted in uncertainties and unpredictable consequences for the affected parties, such as when the wish of the deceased are restricted, equal heirs are treated differently, new forms of inheritance occur or when established protective mechanisms are sidelined. In an age when each person’s right to decide over their own interests enjoys central importance, it can be questioned whether a traditional law of inheritance is effective in contemporary society.The purpose of this dissertation is to examine from a historical perspective to what extent the law of inheritance is adapted to contemporary society, considering changing living conditions, forms of family and societal values. The dissertation’s point of departure is the law of inheritance of 1928 and the law of wills of 1930, and the question of who has the right to inherit and how the estate is distributed. Within this purpose the conditions for inheriting, principles regarding the distribution of the estate and the motives behind these are examined.The research has been conducted through an analysis of the development of the existing inheritance law's design and function in relation to the living conditions, family relationships and social values at different times in history. The approach has required that a wider perspective been applied to the design of the regulations on the right of inheritance and the distribution of the estate, which goes beyond law. The purpose and effect of the mentioned regulations have been identified and analysed on the basis of this background. The approach has meant that the current regulations have been examined both from an internal and an external perspective. The research has resulted in a proposal of change to the present principles of distribution and restrictions in order to accommodate present- day society’s living conditions and forms of family by extending the freedom of the decedent to dispose over the distribution of it’s estate after death.
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| 7. |
- Olsson, Eleonor
(författare)
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Molecular Analysis of Breast Cancer Transcriptomes, Genomes, and Circulating Tumor DNA
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is a very heterogeneous disease in terms of clinical characteristics, genetic aberrations and prognosis. In Paper I, we focused on the CD44 molecule that often is aberrantly expressed in breast cancer and is widely used as a marker for cancer stem cells. Several isoforms of the CD44 molecule were analyzed at the transcriptome level across breast tumors and the expression of individual isoforms was correlated to molecular subtypes, protein expression of clinical markers, and cancer stem cell (CSC) phenotypes in breast tumors and cell lines. The CD44S isoform was associated with expression of the CSC marker ALDH1 and the CSC phenotype CD44+/CD24- was correlated to alternatively spliced isoforms in tumors. The isoforms were differentially expressed in molecular subtypes and HER2 and EGFR positive tumors were associated to CD44S and CD44v8-10, respectively. In Paper II, by using targeted genomic re-sequencing we screened for somatic mutations in 1237 genes in a panel of basal-like breast cancer cell lines, both in coding and surrounding non-coding regions. In total, 658 high confidence SNVs and indels were detected and 315 of these were novel (not in COSMIC). A selection of the variants were validated with Sanger sequencing and, 123 of 130 high confidence variants were confirmed including 111 novel variants. The mutation frequency was higher in coding (CDS) compared to non-coding (non- CDS) regions and in particular G or C base replacements were higher in the CDS compared to non-CDS. The SNVs within the context of T[C]A/T[G]A and T[C]T/A[G]A were significantly more common in the CDS than in the non-CDS regions. Re-sequenced data was used to derive copy number estimations, which correlated well to SNP array data. In Paper III, the potential in using tumor-specific rearrangements present in circulating tumor DNA (ctDNA) to detect occult metastatic breast cancer was evaluated. In total, 14 eventual metastatic (EM) patients and 6 long-term disease free (DF) patients were investigated. We used whole-genome sequencing on the primary tumors to derive patient-specific rearrangements that were confirmed by PCR. Circulating tumor DNA levels across multiple plasma samples during the clinical course were analyzed by quantitative droplet digital PCR. Accurate post-surgical discrimination of EM patients (93%) from DM (100%) was achieved by ctDNA monitoring. The average lead-time to clinical detection of metastatic disease was 11 months (range 0-37 months). Moreover, the ctDNA level was a quantitative predictor for both recurrence (P=0.02) and death (P=0.04). We demonstrated that monitoring of ctDNA can be used for early detection of metastatic breast cancer and is a potential tool for optimization of adjuvant therapy and should be evaluated further in clinical studies.
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| 8. |
- Olsson, Eleonor, et al.
(författare)
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Mutation Screening of 1,237 Cancer Genes across Six Model Cell Lines of Basal-Like Breast Cancer.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Basal-like breast cancer is an aggressive subtype generally characterized as poor prognosis and lacking the expression of the three most important clinical biomarkers, estrogen receptor, progesterone receptor, and HER2. Cell lines serve as useful model systems to study cancer biology in vitro and in vivo. We performed mutational profiling of six basal-like breast cancer cell lines (HCC38, HCC1143, HCC1187, HCC1395, HCC1954, and HCC1937) and their matched normal lymphocyte DNA using targeted capture and next-generation sequencing of 1,237 cancer-associated genes, including all exons, UTRs and upstream flanking regions. In total, 658 somatic variants were identified, of which 378 were non-silent (average 63 per cell line, range 37-146) and 315 were novel (not present in the Catalogue of Somatic Mutations in Cancer database; COSMIC). 125 novel mutations were confirmed by Sanger sequencing (59 exonic, 48 3'UTR and 10 5'UTR, 1 splicing), with a validation rate of 94% of high confidence variants. Of 36 mutations previously reported for these cell lines but not detected in our exome data, 36% could not be detected by Sanger sequencing. The base replacements C/G>A/T, C/G>G/C, C/G>T/A and A/T>G/C were significantly more frequent in the coding regions compared to the non-coding regions (OR 3.2, 95% CI 2.0-5.3, P<0.0001; OR 4.3, 95% CI 2.9-6.6, P<0.0001; OR 2.4, 95% CI 1.8-3.1, P<0.0001; OR 1.8, 95% CI 1.2-2.7, P = 0.024, respectively). The single nucleotide variants within the context of T[C]T/A[G]A and T[C]A/T[G]A were more frequent in the coding than in the non-coding regions (OR 3.7, 95% CI 2.2-6.1, P<0.0001; OR 3.8, 95% CI 2.0-7.2, P = 0.001, respectively). Copy number estimations were derived from the targeted regions and correlated well to Affymetrix SNP array copy number data (Pearson correlation 0.82 to 0.96 for all compared cell lines; P<0.0001). These mutation calls across 1,237 cancer-associated genes and identification of novel variants will aid in the design and interpretation of biological experiments using these six basal-like breast cancer cell lines.
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| 9. |
- Olsson, Eleonor, et al.
(författare)
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Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.
- 2015
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 7:8, s. 1034-1047
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0-37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment.
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| 10. |
- Olsson, Stefan, 1965-, et al.
(författare)
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Sweden
- 2018. - 1
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Ingår i: Corporate Tax Residence and Mobility. - Amsterdam : International Bureau of Fiscal Documentation (IBFD). - 9789087224516 ; , s. 573-590
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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