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1. Supplementary tables S1-S5, S8 and S9 from Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Author

Marchan, Rosemarie, primary, Büttner, Bettina, primary, Lambert, Jörg, primary, Edlund, Karolina, primary, Glaeser, Iris, primary, Blaszkewicz, Meinolf, primary, Leonhardt, Gregor, primary, Marienhoff, Lisa, primary, Kaszta, Darius, primary, Anft, Moritz, primary, Watzl, Carsten, primary, Madjar, Katrin, primary, Grinberg, Marianna, primary, Rempel, Eugen, primary, Hergenröder, Roland, primary, Selinski, Silvia, primary, Rahnenführer, Jörg, primary, Lesjak, Michaela S., primary, Stewart, Joanna D., primary, Cadenas, Cristina, primary, and Hengstler, Jan G., primary

Published
2023
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2. Supplemental methods and figure legends from Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Author

Marchan, Rosemarie, primary, Büttner, Bettina, primary, Lambert, Jörg, primary, Edlund, Karolina, primary, Glaeser, Iris, primary, Blaszkewicz, Meinolf, primary, Leonhardt, Gregor, primary, Marienhoff, Lisa, primary, Kaszta, Darius, primary, Anft, Moritz, primary, Watzl, Carsten, primary, Madjar, Katrin, primary, Grinberg, Marianna, primary, Rempel, Eugen, primary, Hergenröder, Roland, primary, Selinski, Silvia, primary, Rahnenführer, Jörg, primary, Lesjak, Michaela S., primary, Stewart, Joanna D., primary, Cadenas, Cristina, primary, and Hengstler, Jan G., primary

Published
2023
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3. Marchan Supplementary Table 7 from Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Author

Marchan, Rosemarie, primary, Büttner, Bettina, primary, Lambert, Jörg, primary, Edlund, Karolina, primary, Glaeser, Iris, primary, Blaszkewicz, Meinolf, primary, Leonhardt, Gregor, primary, Marienhoff, Lisa, primary, Kaszta, Darius, primary, Anft, Moritz, primary, Watzl, Carsten, primary, Madjar, Katrin, primary, Grinberg, Marianna, primary, Rempel, Eugen, primary, Hergenröder, Roland, primary, Selinski, Silvia, primary, Rahnenführer, Jörg, primary, Lesjak, Michaela S., primary, Stewart, Joanna D., primary, Cadenas, Cristina, primary, and Hengstler, Jan G., primary

Published
2023
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4. CCR Translation for This Article from A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

Author

Schmidt, Marcus, primary, Hellwig, Birte, primary, Hammad, Seddik, primary, Othman, Amnah, primary, Lohr, Miriam, primary, Chen, Zonglin, primary, Boehm, Daniel, primary, Gebhard, Susanne, primary, Petry, Ilka, primary, Lebrecht, Antje, primary, Cadenas, Cristina, primary, Marchan, Rosemarie, primary, Stewart, Joanna D., primary, Solbach, Christine, primary, Holmberg, Lars, primary, Edlund, Karolina, primary, Kultima, Hanna Göransson, primary, Rody, Achim, primary, Berglund, Anders, primary, Lambe, Mats, primary, Isaksson, Anders, primary, Botling, Johan, primary, Karn, Thomas, primary, Müller, Volkmar, primary, Gerhold-Ay, Aslihan, primary, Cotarelo, Christina, primary, Sebastian, Martin, primary, Kronenwett, Ralf, primary, Bojar, Hans, primary, Lehr, Hans-Anton, primary, Sahin, Ugur, primary, Koelbl, Heinz, primary, Gehrmann, Mathias, primary, Micke, Patrick, primary, Rahnenführer, Jörg, primary, and Hengstler, Jan G., primary

Published
2023
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5. Marchan_Supplementary Table 6 from Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Author

Marchan, Rosemarie, primary, Büttner, Bettina, primary, Lambert, Jörg, primary, Edlund, Karolina, primary, Glaeser, Iris, primary, Blaszkewicz, Meinolf, primary, Leonhardt, Gregor, primary, Marienhoff, Lisa, primary, Kaszta, Darius, primary, Anft, Moritz, primary, Watzl, Carsten, primary, Madjar, Katrin, primary, Grinberg, Marianna, primary, Rempel, Eugen, primary, Hergenröder, Roland, primary, Selinski, Silvia, primary, Rahnenführer, Jörg, primary, Lesjak, Michaela S., primary, Stewart, Joanna D., primary, Cadenas, Cristina, primary, and Hengstler, Jan G., primary

Published
2023
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6. Supplementary Materials and Methods from A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

Author

Schmidt, Marcus, primary, Hellwig, Birte, primary, Hammad, Seddik, primary, Othman, Amnah, primary, Lohr, Miriam, primary, Chen, Zonglin, primary, Boehm, Daniel, primary, Gebhard, Susanne, primary, Petry, Ilka, primary, Lebrecht, Antje, primary, Cadenas, Cristina, primary, Marchan, Rosemarie, primary, Stewart, Joanna D., primary, Solbach, Christine, primary, Holmberg, Lars, primary, Edlund, Karolina, primary, Kultima, Hanna Göransson, primary, Rody, Achim, primary, Berglund, Anders, primary, Lambe, Mats, primary, Isaksson, Anders, primary, Botling, Johan, primary, Karn, Thomas, primary, Müller, Volkmar, primary, Gerhold-Ay, Aslihan, primary, Cotarelo, Christina, primary, Sebastian, Martin, primary, Kronenwett, Ralf, primary, Bojar, Hans, primary, Lehr, Hans-Anton, primary, Sahin, Ugur, primary, Koelbl, Heinz, primary, Gehrmann, Mathias, primary, Micke, Patrick, primary, Rahnenführer, Jörg, primary, and Hengstler, Jan G., primary

Published
2023
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7. Supplementary Figures 1-11 from A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

Author

Schmidt, Marcus, primary, Hellwig, Birte, primary, Hammad, Seddik, primary, Othman, Amnah, primary, Lohr, Miriam, primary, Chen, Zonglin, primary, Boehm, Daniel, primary, Gebhard, Susanne, primary, Petry, Ilka, primary, Lebrecht, Antje, primary, Cadenas, Cristina, primary, Marchan, Rosemarie, primary, Stewart, Joanna D., primary, Solbach, Christine, primary, Holmberg, Lars, primary, Edlund, Karolina, primary, Kultima, Hanna Göransson, primary, Rody, Achim, primary, Berglund, Anders, primary, Lambe, Mats, primary, Isaksson, Anders, primary, Botling, Johan, primary, Karn, Thomas, primary, Müller, Volkmar, primary, Gerhold-Ay, Aslihan, primary, Cotarelo, Christina, primary, Sebastian, Martin, primary, Kronenwett, Ralf, primary, Bojar, Hans, primary, Lehr, Hans-Anton, primary, Sahin, Ugur, primary, Koelbl, Heinz, primary, Gehrmann, Mathias, primary, Micke, Patrick, primary, Rahnenführer, Jörg, primary, and Hengstler, Jan G., primary

Published
2023
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8. Supplementary Figures 1 -9 from Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Author

Marchan, Rosemarie, primary, Büttner, Bettina, primary, Lambert, Jörg, primary, Edlund, Karolina, primary, Glaeser, Iris, primary, Blaszkewicz, Meinolf, primary, Leonhardt, Gregor, primary, Marienhoff, Lisa, primary, Kaszta, Darius, primary, Anft, Moritz, primary, Watzl, Carsten, primary, Madjar, Katrin, primary, Grinberg, Marianna, primary, Rempel, Eugen, primary, Hergenröder, Roland, primary, Selinski, Silvia, primary, Rahnenführer, Jörg, primary, Lesjak, Michaela S., primary, Stewart, Joanna D., primary, Cadenas, Cristina, primary, and Hengstler, Jan G., primary

Published
2023
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9. Supplementary Tables 1-3 from A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

Author

Schmidt, Marcus, primary, Hellwig, Birte, primary, Hammad, Seddik, primary, Othman, Amnah, primary, Lohr, Miriam, primary, Chen, Zonglin, primary, Boehm, Daniel, primary, Gebhard, Susanne, primary, Petry, Ilka, primary, Lebrecht, Antje, primary, Cadenas, Cristina, primary, Marchan, Rosemarie, primary, Stewart, Joanna D., primary, Solbach, Christine, primary, Holmberg, Lars, primary, Edlund, Karolina, primary, Kultima, Hanna Göransson, primary, Rody, Achim, primary, Berglund, Anders, primary, Lambe, Mats, primary, Isaksson, Anders, primary, Botling, Johan, primary, Karn, Thomas, primary, Müller, Volkmar, primary, Gerhold-Ay, Aslihan, primary, Cotarelo, Christina, primary, Sebastian, Martin, primary, Kronenwett, Ralf, primary, Bojar, Hans, primary, Lehr, Hans-Anton, primary, Sahin, Ugur, primary, Koelbl, Heinz, primary, Gehrmann, Mathias, primary, Micke, Patrick, primary, Rahnenführer, Jörg, primary, and Hengstler, Jan G., primary

Published
2023
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11. Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

Author

Stewart, Joanna D., Marchan, Rosemarie, Lesjak, Michaela S., Lambert, Joerg, Hergenroeder, Roland, Ellis, James K., Lau, Chung-Ho, Keun, Hector C., Schmitz, Gerd, Schiller, Juergen, Eibisch, Mandy, Hedberg, Christian, Waldmann, Herbert, Lausch, Ekkehart, Tanner, Berno, Sehouli, Jalid, Sagemueller, Jens, Staude, Hagen, Steiner, Eric, and Hengstler, Jan G.

Published
2012

24. LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Author

Cadenas, Cristina, Vosbeck, Sonja, Edlund, Karolina, Grgas, Katharina, Madjar, Katrin, Hellwig, Birte, Adawy, Alshaimaa, Glotzbach, Annika, Stewart, Joanna D., Lesjak, Michaela S., Franckenstein, Dennis, Claus, Maren, Hayen, Heiko, Schriewer, Alexander, Gianmoena, Kathrin, Thaler, Sonja, Schmidt, Marcus, Micke, Patrick, Pontén, Fredrik, Mardinoglu, Adil, Zhang, Cheng, Käfferlein, Heiko U., Watzl, Carsten, Frank, Saša, Rahnenführer, Jörg, Marchan, Rosemarie, Hengstler, Jan G., Cadenas, Cristina, Vosbeck, Sonja, Edlund, Karolina, Grgas, Katharina, Madjar, Katrin, Hellwig, Birte, Adawy, Alshaimaa, Glotzbach, Annika, Stewart, Joanna D., Lesjak, Michaela S., Franckenstein, Dennis, Claus, Maren, Hayen, Heiko, Schriewer, Alexander, Gianmoena, Kathrin, Thaler, Sonja, Schmidt, Marcus, Micke, Patrick, Pontén, Fredrik, Mardinoglu, Adil, Zhang, Cheng, Käfferlein, Heiko U., Watzl, Carsten, Frank, Saša, Rahnenführer, Jörg, Marchan, Rosemarie, and Hengstler, Jan G.

Abstract

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high‐density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis‐free survival in node‐negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress‐induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.

Published
2019
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25. LIPG‐promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Author

Cadenas, Cristina, primary, Vosbeck, Sonja, additional, Edlund, Karolina, additional, Grgas, Katharina, additional, Madjar, Katrin, additional, Hellwig, Birte, additional, Adawy, Alshaimaa, additional, Glotzbach, Annika, additional, Stewart, Joanna D., additional, Lesjak, Michaela S., additional, Franckenstein, Dennis, additional, Claus, Maren, additional, Hayen, Heiko, additional, Schriewer, Alexander, additional, Gianmoena, Kathrin, additional, Thaler, Sonja, additional, Schmidt, Marcus, additional, Micke, Patrick, additional, Pontén, Fredrik, additional, Mardinoglu, Adil, additional, Zhang, Cheng, additional, Käfferlein, Heiko U., additional, Watzl, Carsten, additional, Frank, Saša, additional, Rahnenführer, Jörg, additional, Marchan, Rosemarie, additional, and Hengstler, Jan G., additional

Published
2019
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26. Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Author

Marchan, Rosemarie, primary, Büttner, Bettina, additional, Lambert, Jörg, additional, Edlund, Karolina, additional, Glaeser, Iris, additional, Blaszkewicz, Meinolf, additional, Leonhardt, Gregor, additional, Marienhoff, Lisa, additional, Kaszta, Darius, additional, Anft, Moritz, additional, Watzl, Carsten, additional, Madjar, Katrin, additional, Grinberg, Marianna, additional, Rempel, Eugen, additional, Hergenröder, Roland, additional, Selinski, Silvia, additional, Rahnenführer, Jörg, additional, Lesjak, Michaela S., additional, Stewart, Joanna D., additional, Cadenas, Cristina, additional, and Hengstler, Jan G., additional

Published
2017
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29. A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin ? C as a compatible prognostic marker in human solid tumors

Author

Schmidt, Marcus, Hellwig, Birte, Hammad, Seddik, Othman, Amnah, Lohr, Miriam, Chen, Zonglin, Boehm, Daniel, Gebhard, Susanne, Petry, Ilka, Lebrecht, Antje, Cadenas, Cristina, Marchan, Rosemarie, Stewart, Joanna D, Solbach, Christine, Holmberg, Lars, Edlund, Karolina, Kultima, Hanna Göransson, Rody, Achim, Berglund, Anders, Lambe, Mats, Isaksson, Anders, Botling, Johan, Karn, Thomas, Müller, Volkmar, Gerhold-Ay, Aslihan, Cotarelo, Christina, Sebastian, Martin, Kronenwett, Ralf, Bojar, Hans, Lehr, Hans-Anton, Sahin, Ugur, Koelbl, Heinz, Gehrmann, Mathias, Micke, Patrick, Rahnenführer, Jörg, and Hengstler, Jan G

Abstract

Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anticancer therapy. It could be validated in several independent cohorts and carried out similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.

Published
2012

31. POLG determines the risk of sodium valproate induced liver toxicity

Author

Stewart, Joanna D., Horvath, Rita, Baruffini, Enrico, Ferrero, Iliana, Bulst, Stefanie, Watkins, Paul B., Fontana, Robert J., Day, Christopher P., and Chinnery, Patrick F.

Subjects
Adult, Bipolar Disorder, Adolescent, GABA Agents, Valproic Acid, Headache, Genetic Variation, Diffuse Cerebral Sclerosis of Schilder, DNA-Directed DNA Polymerase, Middle Aged, Polymorphism, Single Nucleotide, Risk Assessment, Article, DNA Polymerase gamma, Young Adult, Amino Acid Substitution, Liver, Seizures, Child, Preschool, Hepatocytes, Humans, lipids (amino acids, peptides, and proteins), Child
Abstract

Sodium valproate (VPA) is widely used throughout the world to treat epilepsy, migraine, chronic headache, bipolar disorder, and as adjuvant chemotherapy. VPA toxicity is an uncommon but potentially fatal cause of idiosyncratic liver injury. Rare mutations in POLG, which codes for the mitochondrial DNA polymerase γ (polγ), cause Alpers-Huttenlocher syndrome (AHS). AHS is a neurometabolic disorder associated with an increased risk of developing fatal VPA hepatotoxicity. We therefore set out to determine whether common genetic variants in POLG explain why some otherwise healthy individuals develop VPA hepatotoxicity. We carried out a prospective study of subjects enrolled in the Drug Induced Liver Injury Network (DILIN) from 2004 to 2008 through five US centers. POLG was sequenced and the functional consequences of VPA and novel POLG variants were evaluated in primary human cell lines and the yeast model system Saccharomyces cerevisiae. Heterozygous genetic variation in POLG was strongly associated with VPA-induced liver toxicity (odds ratio = 23.6, 95% confidence interval [CI] = 8.4-65.8, P = 5.1 × 10⁻⁷). This was principally due to the p.Q1236H substitution which compromised polγ function in yeast. Therapeutic doses of VPA inhibited human cellular proliferation and high doses caused nonapoptotic cell death, which was not mediated through mitochondrial DNA depletion, mutation, or a defect of fatty acid metabolism.These findings implicate impaired liver regeneration in VPA toxicity and show that prospective genetic testing of POLG will identify individuals at high risk of this potentially fatal consequence of treatment.

Published
2010

33. Microarrays for the scalable production of metabolically relevant tumour spheroids: a tool for modulating chemosensitivity traits

Author

Hardelauf, Heike, Frimat, Jean-Philippe, Stewart, Joanna D., Schormann, Wiebke, Chiang, Ya-Yu, Lampen, Peter, Franzke, Joachim, Hengstler, Jan G., Cadenas, Cristina, Kunz-Schughart, Leoni A., West, Jonathan, Hardelauf, Heike, Frimat, Jean-Philippe, Stewart, Joanna D., Schormann, Wiebke, Chiang, Ya-Yu, Lampen, Peter, Franzke, Joachim, Hengstler, Jan G., Cadenas, Cristina, Kunz-Schughart, Leoni A., and West, Jonathan

Abstract

We report the use of thin film poly(dimethylsiloxane) (PDMS) prints for the arrayed mass production of highly uniform 3-D human HT29 colon carcinoma spheroids. The spheroids have an organotypic density and, as determined by 3-axis imaging, were genuinely spherical. Critically, the array density impacts growth kinetics and can be tuned to produce spheroids ranging in diameter from 200 to 550 µm. The diffusive limit of competition for media occurred with a pitch of ≥1250 µm and was used for the optimal array-based culture of large, viable spheroids. During sustained culture mass transfer gradients surrounding and within the spheroids are established, and lead to growth cessation, altered expression patterns and the formation of a central secondary necrosis. These features reflect the microenvironment of avascularised tumours, making the array format well suited for the production of model tumours with defined sizes and thus defined spatio-temporal pathophysiological gradients. Experimental windows, before and after the onset of hypoxia, were identified and used with an enzyme activity-based viability assay to measure the chemosensitivity towards irinotecan. Compared to monolayer cultures, a marked reduction in the drug efficacy towards the different spheroid culture states was observed and attributed to cell cycle arrest, the 3-D character, scale and/or hypoxia factors. In summary, spheroid culture using the array format has great potential to support drug discovery and development, as well as tumour biology research., Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Published
2014

35. Whole Cell Quenched Flow Analysis

Author

Chiang, Ya-Yu, primary, Haeri, Sina, additional, Gizewski, Carsten, additional, Stewart, Joanna D., additional, Ehrhard, Peter, additional, Shrimpton, John, additional, Janasek, Dirk, additional, and West, Jonathan, additional

Published
2013
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37. Immunoglobulin Kappa C Predicts Overall Survival in Node-Negative Breast Cancer

Author

Chen, Zonglin, primary, Gerhold-Ay, Aslihan, additional, Gebhard, Susanne, additional, Boehm, Daniel, additional, Solbach, Christine, additional, Lebrecht, Antje, additional, Battista, Marco, additional, Sicking, Isabel, additional, Cotarelo, Christina, additional, Cadenas, Cristina, additional, Marchan, Rosemarie, additional, Stewart, Joanna D., additional, Gehrmann, Mathias, additional, Koelbl, Heinz, additional, Hengstler, Jan G., additional, and Schmidt, Marcus, additional

Published
2012
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39. A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

Author

Schmidt, Marcus, primary, Hellwig, Birte, additional, Hammad, Seddik, additional, Othman, Amnah, additional, Lohr, Miriam, additional, Chen, Zonglin, additional, Boehm, Daniel, additional, Gebhard, Susanne, additional, Petry, Ilka, additional, Lebrecht, Antje, additional, Cadenas, Cristina, additional, Marchan, Rosemarie, additional, Stewart, Joanna D., additional, Solbach, Christine, additional, Holmberg, Lars, additional, Edlund, Karolina, additional, Kultima, Hanna Göransson, additional, Rody, Achim, additional, Berglund, Anders, additional, Lambe, Mats, additional, Isaksson, Anders, additional, Botling, Johan, additional, Karn, Thomas, additional, Müller, Volkmar, additional, Gerhold-Ay, Aslihan, additional, Cotarelo, Christina, additional, Sebastian, Martin, additional, Kronenwett, Ralf, additional, Bojar, Hans, additional, Lehr, Hans-Anton, additional, Sahin, Ugur, additional, Koelbl, Heinz, additional, Gehrmann, Mathias, additional, Micke, Patrick, additional, Rahnenführer, Jörg, additional, and Hengstler, Jan G., additional

Published
2012
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40. Microarrays for the scalable production of metabolically relevant tumour spheroids: a tool for modulating chemosensitivity traits

Author

Hardelauf, Heike, primary, Frimat, Jean-Philippe, additional, Stewart, Joanna D., additional, Schormann, Wiebke, additional, Chiang, Ya-Yu, additional, Lampen, Peter, additional, Franzke, Joachim, additional, Hengstler, Jan G., additional, Cadenas, Cristina, additional, Kunz-Schughart, Leoni A., additional, and West, Jonathan, additional

Published
2011
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42. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance

Author

Hudson, Gavin, primary, Amati-Bonneau, Patrizia, additional, Blakely, Emma L., additional, Stewart, Joanna D., additional, He, Langping, additional, Schaefer, Andrew M., additional, Griffiths, Philip G., additional, Ahlqvist, Kati, additional, Suomalainen, Anu, additional, Reynier, Pascal, additional, McFarland, Robert, additional, Turnbull, Douglass M., additional, Chinnery, Patrick F., additional, and Taylor, Robert W., additional

Published
2007
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44. Immunoglobulin Kappa C Predicts Overall Survival in Node-Negative Breast Cancer.

Author

Zonglin Chen, Gerhold-Ay, Aslihan, Gebhard, Susanne, Boehm, Daniel, Solbach, Christine, Lebrecht, Antje, Battista, Marco, Sicking, Isabel, Cotarelo, Christina, Cadenas, Cristina, Marchan, Rosemarie, Stewart, Joanna D., Gehrmann, Mathias, Koelbl, Heinz, Hengstler, Jan G., Schmidt, Marcus, and Lafrenie, Robert

Subjects
IMMUNOGLOBULINS, BLOOD proteins, BREAST cancer research, BIOMARKERS, GENETIC markers, GENE expression
Abstract

Background: Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed the association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients. Material and Methods: IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status. Results: 160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantly associated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360-0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233-0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315-0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196-0.705). Conclusion: Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer. [ABSTRACT FROM AUTHOR]

Published
2012
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45. MFN2 mutations cause compensatory mitochondrial DNA proliferation

Author

Sitarz, Kamil S, Yu-Wai-Man, Patrick, Pyle, Angela, Stewart, Joanna D, Rautenstrauss, Bernd, Seeman, Pavel, Reilly, Mary M, Horvath, Rita, and Chinnery, Patrick F

Subjects
Male, Mitochondrial Proteins, Optic Atrophy, Humans, Mitochondrial Myopathies, Female, DNA, Mitochondrial, 3. Good health, GTP Phosphohydrolases

46. Clonally Expanded Mitochondrial DNA Mutations in Epileptic Individuals With Mutated DNA Polymerase {gamma}

Author

Zsurka, Gábor, Baron, Miriam, Stewart, Joanna D., Kornblum, Cornelia, Bös, Monika, Sassen, Robert, Taylor, Robert W., Elger, Christian E., Chinnery, Patrick F., and Kunz, Wolfram S.

Abstract

The instability of the mitochondrial genome in individuals harboring pathogenic mutations in the catalytic subunit of mitochondrial DNA (mtDNA) polymerase γ (POLG) is well recognized, but the underlying molecular mechanisms remain to be elucidated. In 5 pediatric patients with severe myoclonic epilepsy and valproic acid-induced liver failure, we identified 1 novel and 4 previously described pathogenic mutations in the linker region of this enzyme. Although muscle biopsies in these patients showed unremarkable histologic features, postmortem liver tissue available from 1 individual exhibited large cytochrome c oxidase-negative areas. These cytochrome c oxidase-negative areas contained 4-fold less mtDNA than cytochrome c oxidase-positive areas. Decreased copy numbers of mtDNA were observed not only in the liver, skeletal muscle, and brain but also in blood samples from all patients. There were also patient-specific patterns of multiple mtDNA deletions in different tissues, and in 2 patients, there were clonally expanded mtDNA point mutations. The low amount of deleted mtDNA molecules makes it unlikely that the deletions contribute significantly to the general biochemical defect. The clonal expansion of a few individual-specific deletions and point mutations indicates an accelerated segregation of early mtDNA mutations that likely are a consequence of low mtDNA copy numbers. Moreover, these results suggest a potential diagnostic approach for identifying mtDNA depletion in patients.

Published
2008
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