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Koos, Björn
Publications (5 of 5) Show all publications
Koechling, M., Ewelt, C., Fuertjes, G., Peetz-Dienhart, S., Koos, B., Hasselblatt, M., . . . Brokinkel, B. (2016). hTERT promoter methylation in pituitary adenomas. BRAIN TUMOR PATHOLOGY, 33(1), 27-34
Open this publication in new window or tab >>hTERT promoter methylation in pituitary adenomas
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2016 (English)In: BRAIN TUMOR PATHOLOGY, ISSN 1433-7398, Vol. 33, no 1, p. 27-34Article in journal (Refereed) Published
Abstract [en]

Telomerase reverse transcriptase (TERT) expression is a hallmark in tumorigenesis and upregulated due to mutations and methylation of the human (h)TERT promoter. As mutations are rare but methylation is common in pituitary adenomas (PA), we determined promoter methylation and its clinical impact in 85 primary and 15 recurrent PA by methylation-specific PCR. 40 females (47 %) and 45 males (53 %) with a median age of 53 years harboring micro-, macro-, and giant adenomas in 12, 82, and 6 % were included (prolactinomas, corticotroph, somatotroph, gonadotroph, thyreotroph, plurihormonal, and null cell adenomas in 11, 18, 10, 29, 1, 10, and 21 %, respectively). In primary diagnosed tumors, methylation rate was 27 % and higher in males than in females (40 vs. 13 %, p = 0.001) after uni- and multivariate analyses. Methylation differed among PA subtypes (0-42 %, p = n.s.) and was not significantly correlated with tumor size, cavernous sinus invasion, or serum hormone levels. Ki67 labeling index and recurrence (N = 16, 19 %) were independent of methylation. In recurrent tumors, methylation was similar to primary PA (N = 5/15, 33 %) and remained unchanged along follow-up. Thus, while being commonly observed in PA, hTERT promoter methylation is stable along follow-up and independent of most clinical variables, PA subtype, proliferation, and without prognostic value.

Keywords
Pituitary adenomas, Epigenetics, hTERT promoter, Methylation, Telomerase
National Category
Cancer and Oncology Neurology
Identifiers
urn:nbn:se:uu:diva-275560 (URN)10.1007/s10014-015-0230-8 (DOI)000367694800004 ()26390879 (PubMedID)
Available from: 2016-02-04 Created: 2016-02-04 Last updated: 2016-02-04Bibliographically approved
Hasselblatt, M., Jeibmann, A., Eikmeier, K., Linge, A., Johann, P., Koos, B., . . . Paulus, W. (2014). Hippo Signaling is Essential for the Phenotype Associated with Snr1 Loss in Drosophila Melanogastera and Involved in the Biology of Smarcb1-Deficient Atypical Teratoid/Rhabdoid Tumors. Paper presented at 16th International Symposium on Pediatric Neuro-Oncology (ISPNO), JUN 28-JUL 02, 2014, Singapore, SINGAPORE. Neuro-Oncology, 16, 3-4
Open this publication in new window or tab >>Hippo Signaling is Essential for the Phenotype Associated with Snr1 Loss in Drosophila Melanogastera and Involved in the Biology of Smarcb1-Deficient Atypical Teratoid/Rhabdoid Tumors
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2014 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 16, p. 3-4Article in journal, Meeting abstract (Other academic) Published
National Category
Neurology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-229382 (URN)000337924200013 ()
Conference
16th International Symposium on Pediatric Neuro-Oncology (ISPNO), JUN 28-JUL 02, 2014, Singapore, SINGAPORE
Available from: 2014-08-06 Created: 2014-08-06 Last updated: 2017-12-05Bibliographically approved
Jeibmann, A., Eikmeier, K., Linge, A., Kool, M., Koos, B., Schulz, J., . . . Hasselblatt, M. (2014). Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster. Nature Communications, 5, 4005
Open this publication in new window or tab >>Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster
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2014 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, p. 4005-Article in journal (Refereed) Published
Abstract [en]

Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.

National Category
Medical Genetics Basic Medicine
Identifiers
urn:nbn:se:uu:diva-230528 (URN)10.1038/ncomms5005 (DOI)000338836200002 ()
Available from: 2014-08-28 Created: 2014-08-26 Last updated: 2018-01-11Bibliographically approved
Weibrecht, I., Lundin, E., Kiflemariam, S., Mignardi, M., Grundberg, I., Larsson, C., . . . Söderberg, O. (2013). In situ detection of individual mRNA molecules and protein complexes or post-translational modifications using padlock probes combined with the in situ proximity ligation assay. Nature Protocols, 8(2), 355-372
Open this publication in new window or tab >>In situ detection of individual mRNA molecules and protein complexes or post-translational modifications using padlock probes combined with the in situ proximity ligation assay
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2013 (English)In: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 8, no 2, p. 355-372Article in journal (Refereed) Published
Abstract [en]

Analysis at the single-cell level is essential for the understanding of cellular responses in heterogeneous cell populations, but it has been difficult to perform because of the strict requirements put on detection methods with regard to selectivity and sensitivity (i.e., owing to the cross-reactivity of probes and limited signal amplification). Here we describe a 1.5-d protocol for enumerating and genotyping mRNA molecules in situ while simultaneously obtaining information on protein interactions or post-translational modifications; this is achieved by combining padlock probes with in situ proximity ligation assays (in situ PLA). In addition, we provide an example of how to design padlock probes and how to optimize staining conditions for fixed cells and tissue sections. Both padlock probes and in situ PLA provide the ability to directly visualize single molecules by standard microscopy in fixed cells or tissue sections, and these methods may thus be valuable for both research and diagnostic purposes.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-199740 (URN)10.1038/nprot.2013.006 (DOI)000317109900009 ()
Available from: 2013-05-13 Created: 2013-05-13 Last updated: 2017-12-06Bibliographically approved
Koos, B., Cane, G., Grannas, K., Clausson, C.-M., Arngården, L., Klaesson, A. & Söderberg, O.Proximity Depended Initiation of Hybridization Chain Reaction.
Open this publication in new window or tab >>Proximity Depended Initiation of Hybridization Chain Reaction
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Sensitive detection of protein interactions and post-translational modifications of native proteins is a challenge for research and diagnostic purposes. A method for this, which could be used in point of care devices should be cheap and robust.

Results: Building on hybridization chain reaction, we designed a four hairpin system which is metastable in solution at 37°C for several hours and undergoes rapid signal amplification upon introduction of an initiator oligonucleotide. When the proximity hairpins are conjugated to antibodies these proximity probes in combination with the HCR hairpins and the initiator oligonucleotide provide a specific, enzyme free method to detect HIF-1α/HIF-1β and potentially other protein interactions and PTMs in situ. Furthermore it was possible to detect single proteins in the different compartments of the cell, further proving the specificity of this technique.

Conclusion: In this study we present proximity dependent HCR, which is a cheap and robust method to detect protein interactions and post-translational modifications. Because of its independence from enzymes the technique has only low demands on storage and handling which makes it interesting for point of care devices.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-218249 (URN)
Available from: 2014-02-10 Created: 2014-02-10 Last updated: 2018-01-11Bibliographically approved
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