13 results on '"Stadtler, Nadine"'
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2. Clinical and pathological characteristics of familial melanoma with germline <scp> TERT </scp> promoter variants
- Author
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Zaremba-Montenari, Anne, Meier, Friedegund, Schlein, Christian, Jansen, Philipp, Lodde, Georg, Song, Mingxia, Kretz, Julia, Möller, Inga, Stadtler, Nadine, Livingstone, Elisabeth, Zimmer, Lisa, Hadaschik, Eva, Sucker, Antje, Schadendorf, Dirk, and Griewank, Klaus
- Subjects
Adult ,Proto-Oncogene Proteins B-raf ,Skin Neoplasms ,Adolescent ,Medizin ,Dermatology ,Middle Aged ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,Oncology ,Mutation ,Imatinib Mesylate ,Humans ,Immune Checkpoint Inhibitors ,Telomerase ,Melanoma - Abstract
Around 10% of melanoma occurs in patients with a suspected familial predisposition. TERT promoter mutations are the most common somatic hotspot mutations in human cancers. However, only two families with germline mutations have been identified to date. We present detailed histological, clinical, and molecular pathologic analyses of affected patients and details of newly identified individuals in one of these previously reported families. TERT (NM_198253.3) Chr.5:1,295,161Tgt;C (c.-57 Tgt;C) promoter variants were detected in all melanoma-affected (n = 18) and one non-diseased family member. The median age at diagnosis was 30 years (n = 18, range 16-46 years, 2 unknown). While most primary melanomas arose on the upper extremities (n = 7, 21%) and were superficial spreading melanoma (SSM, n = 8, 24%), many primary melanomas also originated from non-UV-exposed mucosal (n = 2, 6%) and acral (n = 4, 12%) locations. One SSM sample harbored a Chr.5:1,295,228Cgt;T TERT promoter mutation in addition to the germline Chr.5:1,295,161Tgt;C variant, arguing additional pathway activation can support tumor pathogenesis. Patients treated with BRAF inhibitor and/or immune checkpoint inhibition (ICI) showed responses, although of limited duration. One mucosal melanoma harbored both a KIT copy number gain and an activating c.1727 p.Leu576Pro mutation. Following the modest response to ICI, subsequent KIT inhibitor (imatinib) therapy demonstrated an ongoing complete pathological response (currently 7 months).
- Published
- 2022
- Full Text
- View/download PDF
3. Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system
- Author
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van de Nes, Johannes, Gessi, Marco, Sucker, Antje, Möller, Inga, Stiller, Mathias, Horn, Susanne, Scholz, Simone L., Pischler, Carina, Stadtler, Nadine, Schilling, Bastian, Zimmer, Lisa, Hillen, Uwe, Scolyer, Richard A., Buckland, Michael E., Lauriola, Libero, Pietsch, Torsten, Waha, Andreas, Schadendorf, Dirk, Murali, Rajmohan, and Griewank, Klaus G.
- Published
- 2016
- Full Text
- View/download PDF
4. Genetic and Methylation Analysis of CTNNB1 in Benign and Malignant Melanocytic Lesions
- Author
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Zaremba, Anne, primary, Jansen, Philipp, additional, Murali, Rajmohan, additional, Mayakonda, Anand, additional, Riedel, Anna, additional, Krahl, Dieter, additional, Burkhardt, Hans, additional, John, Stefan, additional, Géraud, Cyrill, additional, Philip, Manuel, additional, Kretz, Julia, additional, Möller, Inga, additional, Stadtler, Nadine, additional, Sucker, Antje, additional, Paschen, Annette, additional, Ugurel, Selma, additional, Zimmer, Lisa, additional, Livingstone, Elisabeth, additional, Horn, Susanne, additional, Plass, Christoph, additional, Schadendorf, Dirk, additional, Hadaschik, Eva, additional, Lutsik, Pavlo, additional, and Griewank, Klaus, additional
- Published
- 2022
- Full Text
- View/download PDF
5. Clinical and pathological characteristics of familial melanoma with germlineTERTpromoter variants
- Author
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Zaremba, Anne, primary, Meier, Friedegund, additional, Schlein, Christian, additional, Jansen, Philipp, additional, Lodde, Georg, additional, Song, Mingxia, additional, Kretz, Julia, additional, Möller, Inga, additional, Stadtler, Nadine, additional, Livingstone, Elisabeth, additional, Zimmer, Lisa, additional, Hadaschik, Eva, additional, Sucker, Antje, additional, Schadendorf, Dirk, additional, and Griewank, Klaus, additional
- Published
- 2022
- Full Text
- View/download PDF
6. Genetic and methylation profiles distinguish benign, malignant and spitzoid melanocytic tumors
- Author
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Zaremba, Anne, primary, Jansen, Philipp, additional, Murali, Rajmohan, additional, Mayakonda, Anand, additional, Riedel, Anna, additional, Philip, Manuel, additional, Rose, Christian, additional, Schaller, Jörg, additional, Müller, Hansgeorg, additional, Kutzner, Heinz, additional, Möller, Inga, additional, Stadtler, Nadine, additional, Kretz, Julia, additional, Sucker, Antje, additional, Bankfalvi, Agnes, additional, Livingstone, Elisabeth, additional, Zimmer, Lisa, additional, Horn, Susanne, additional, Paschen, Annette, additional, Plass, Christoph, additional, Schadendorf, Dirk, additional, Hadaschik, Eva, additional, Lutsik, Pavlo, additional, and Griewank, Klaus, additional
- Published
- 2022
- Full Text
- View/download PDF
7. Genetic and Methylation Analysis of CTNNB1 in Benign and Malignant Melanocytic Lesions
- Author
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Zaremba, Anne, Jansen, Philipp, Murali, Rajmohan, Mayakonda, Anand, Riedel, Anna, Krahl, Dieter, Burkhardt, Hans, John, Stefan, Géraud, Cyrill, Philip, Manuel, Kretz, Julia, Möller, Inga, Stadtler, Nadine, Sucker, Antje, Paschen, Annette, Ugurel, Selma, Zimmer, Lisa, Livingstone, Elisabeth, Horn, Susanne, Plass, Christoph, Schadendorf, Dirk, Hadaschik, Eva, Lutsik, Pavlo, Griewank, Klaus, Zaremba, Anne, Jansen, Philipp, Murali, Rajmohan, Mayakonda, Anand, Riedel, Anna, Krahl, Dieter, Burkhardt, Hans, John, Stefan, Géraud, Cyrill, Philip, Manuel, Kretz, Julia, Möller, Inga, Stadtler, Nadine, Sucker, Antje, Paschen, Annette, Ugurel, Selma, Zimmer, Lisa, Livingstone, Elisabeth, Horn, Susanne, Plass, Christoph, Schadendorf, Dirk, Hadaschik, Eva, Lutsik, Pavlo, and Griewank, Klaus
- Abstract
Melanocytic neoplasms have been genetically characterized in detail during the last decade. Recurrent CTNNB1 exon 3 mutations have been recognized in the distinct group of melanocytic tumors showing deep penetrating nevus-like morphology. In addition, they have been identified in 1–2% of advanced melanoma. Performing a detailed genetic analysis of difficult-to-classify nevi and melanomas with CTNNB1 mutations, we found that benign tumors (nevi) show characteristic morphological, genetic and epigenetic traits, which distinguish them from other nevi and melanoma. Malignant CTNNB1-mutant tumors (melanomas) demonstrated a different genetic profile, instead grouping clearly with other non-CTNNB1 melanomas in methylation assays. To further evaluate the role of CTNNB1 mutations in melanoma, we assessed a large cohort of clinically sequenced melanomas, identifying 38 tumors with CTNNB1 exon 3 mutations, including recurrent S45 (n = 13, 34%), G34 (n = 5, 13%), and S27 (n = 5, 13%) mutations. Locations and histological subtype of CTNNB1-mutated melanoma varied; none were reported as showing deep penetrating nevus-like morphology. The most frequent concurrent activating mutations were BRAF V600 (n = 21, 55%) and NRAS Q61 (n = 13, 34%). In our cohort, four of seven (58%) and one of nine (11%) patients treated with targeted therapy (BRAF and MEK Inhibitors) or immune-checkpoint therapy, respectively, showed disease control (partial response or stable disease). In summary, CTNNB1 mutations are associated with a unique melanocytic tumor type in benign tumors (nevi), which can be applied in a diagnostic setting. In advanced disease, no clear characteristics distinguishing CTNNB1-mutant from other melanomas were observed; however, studies of larger, optimally prospective, cohorts are warranted.
- Published
- 2022
8. Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition — A Descriptive Observational Retrospective Multicenter Analysis
- Author
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Zaremba, Anne, Kramer, Rafaela, De Temple, Viola, Bertram, Stefanie, Salzmann, Martin, Gesierich, Anja, Reinhardt, Lydia, Baroudjian, Barouyr, Sachse, Michael M., Mechtersheimer, Gunhild, Johnson, Douglas B., Weppler, Alison M., Spain, Lavinia, Loquai, Carmen, Dudda, Milena, Pföhler, Claudia, Hepner, Adriana, Long, Georgina V., Menzies, Alexander M., Carlino, Matteo S., Lebbé, Céleste, Enokida, Tomohiro, Tahara, Makoto, Bröckelmann, Paul J., Eigentler, Thomas, Kähler, Katharina C., Gutzmer, Ralf, Berking, Carola, Ugurel, Selma, Stadtler, Nadine, Sucker, Antje, Becker, Jürgen, Livingstone, Elisabeth, Meier, Friedegund, Hassel, Jessica C., Schadendorf, Dirk, Hanoun, Maher, Heinzerling, Lucie, and Zimmer, Lisa
- Subjects
Medizinische Fakultät » Universitätsklinikum Essen » Westdeutsches Tumorzentrum Essen (WTZ) » Pädiatrische Hämatologie/Onkologie ,Medizinische Fakultät » Universitätsklinikum Essen » Institut für Pathologie und Neuropathologie ,Oncology ,Medizin ,malignant melanoma ,immune checkpoint inhibition ,neutropenia ,ddc:610 ,Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Dermatologie ,adverse events ,Original Research ,hematotoxicity - Abstract
Introduction: Immune checkpoint inhibitors (ICI) are increasingly being used to treat numerous cancer types. Together with improved recognition of toxicities, this has led to more frequent identification of rare immune-related adverse events (irAE), for which specific treatment strategies are needed. Neutropenia is a rare hematological irAE that has a potential for a high mortality rate because of its associated risk of sepsis. Prompt recognition and timely treatment of this life-threatening irAE are therefore critical to the outcome of patients with immune-related neutropenia. Methods: This multicenter international retrospective study was conducted at 17 melanoma centers to evaluate the clinical characteristics, diagnostics, treatment, and outcomes of melanoma patients with grade 4 neutropenia (
- Published
- 2021
9. Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition — A Descriptive Observational Retrospective Multicenter Analysis
- Author
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Zaremba, Anne, primary, Kramer, Rafaela, additional, De Temple, Viola, additional, Bertram, Stefanie, additional, Salzmann, Martin, additional, Gesierich, Anja, additional, Reinhardt, Lydia, additional, Baroudjian, Barouyr, additional, Sachse, Michael M., additional, Mechtersheimer, Gunhild, additional, Johnson, Douglas B., additional, Weppler, Alison M., additional, Spain, Lavinia, additional, Loquai, Carmen, additional, Dudda, Milena, additional, Pföhler, Claudia, additional, Hepner, Adriana, additional, Long, Georgina V., additional, Menzies, Alexander M., additional, Carlino, Matteo S., additional, Lebbé, Céleste, additional, Enokida, Tomohiro, additional, Tahara, Makoto, additional, Bröckelmann, Paul J., additional, Eigentler, Thomas, additional, Kähler, Katharina C., additional, Gutzmer, Ralf, additional, Berking, Carola, additional, Ugurel, Selma, additional, Stadtler, Nadine, additional, Sucker, Antje, additional, Becker, Jürgen C., additional, Livingstone, Elisabeth, additional, Meier, Friedegund, additional, Hassel, Jessica C., additional, Schadendorf, Dirk, additional, Hanoun, Maher, additional, Heinzerling, Lucie, additional, and Zimmer, Lisa, additional
- Published
- 2021
- Full Text
- View/download PDF
10. Clinical and pathological characteristics of familial melanoma with germline TERT promoter variants.
- Author
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Zaremba, Anne, Meier, Friedegund, Schlein, Christian, Jansen, Philipp, Lodde, Georg, Song, Mingxia, Kretz, Julia, Möller, Inga, Stadtler, Nadine, Livingstone, Elisabeth, Zimmer, Lisa, Hadaschik, Eva, Sucker, Antje, Schadendorf, Dirk, and Griewank, Klaus
- Subjects
IMMUNE checkpoint inhibitors ,MELANOMA ,GERM cells ,FORELIMB - Abstract
Around 10% of melanoma occurs in patients with a suspected familial predisposition. TERT promoter mutations are the most common somatic hotspot mutations in human cancers. However, only two families with germline mutations have been identified to date. We present detailed histological, clinical, and molecular pathologic analyses of affected patients and details of newly identified individuals in one of these previously reported families. TERT (NM_198253.3) Chr.5:1,295,161T>C (c.‐57 T>C) promoter variants were detected in all melanoma‐affected (n = 18) and one non‐diseased family member. The median age at diagnosis was 30 years (n = 18, range 16–46 years, 2 unknown). While most primary melanomas arose on the upper extremities (n = 7, 21%) and were superficial spreading melanoma (SSM, n = 8, 24%), many primary melanomas also originated from non‐UV‐exposed mucosal (n = 2, 6%) and acral (n = 4, 12%) locations. One SSM sample harbored a Chr.5:1,295,228C>T TERT promoter mutation in addition to the germline Chr.5:1,295,161T>C variant, arguing additional pathway activation can support tumor pathogenesis. Patients treated with BRAF inhibitor and/or immune checkpoint inhibition (ICI) showed responses, although of limited duration. One mucosal melanoma harbored both a KIT copy number gain and an activating c.1727 p.Leu576Pro mutation. Following the modest response to ICI, subsequent KIT inhibitor (imatinib) therapy demonstrated an ongoing complete pathological response (currently 7 months). [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Acquired IFNγ 3 resistance impairs anti-Tumor immunity and gives rise to T-cell-resistant melanoma lesions
- Author
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Sucker, Antje, Zhao, Fang, Pieper, Natalia, Heeke, Christina, Maltaner, Raffaela, Stadtler, Nadine, Real, Birgit, Bielefeld, Nicola, Howe, Sebastian, Weide, Benjamin, Gutzmer, Ralf, Utikal, Jochen, Loquai, Carmen, Gogas, Helen, Klein-Hitpaß, Ludger, Zeschnigk, Michael, Westendorf, Astrid, Trilling, Mirko, Horn, Susanne, Schilling, Bastian, Schadendorf, Dirk, Griewank, Klaus, and Paschen, Annette
- Subjects
Medizin - Abstract
Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFN 3 secretion by CD8 + T cells is critical for therapy efficacy having anti-proliferative and pro-Apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFN 3 resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFN 3 signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-Tumour IFN 3 activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFN 3. Allelic JAK1/2 losses predisposing to IFN 3 resistance development are frequent in melanoma. Subclones harbouring inactivating mutations emerge under various immunotherapies but are also detectable in pre-Treatment biopsies. Our data demonstrate that JAK1/2 deficiency protects melanoma from anti-Tumour IFN 3 activity and results in T-cell-resistant HLA class I-negative lesions. Screening for mechanisms of IFN 3 resistance should be considered in therapeutic decision-making. CA Paschen
- Published
- 2017
12. Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions
- Author
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Sucker, Antje, primary, Zhao, Fang, additional, Pieper, Natalia, additional, Heeke, Christina, additional, Maltaner, Raffaela, additional, Stadtler, Nadine, additional, Real, Birgit, additional, Bielefeld, Nicola, additional, Howe, Sebastian, additional, Weide, Benjamin, additional, Gutzmer, Ralf, additional, Utikal, Jochen, additional, Loquai, Carmen, additional, Gogas, Helen, additional, Klein-Hitpass, Ludger, additional, Zeschnigk, Michael, additional, Westendorf, Astrid M., additional, Trilling, Mirko, additional, Horn, Susanne, additional, Schilling, Bastian, additional, Schadendorf, Dirk, additional, Griewank, Klaus G., additional, and Paschen, Annette, additional
- Published
- 2017
- Full Text
- View/download PDF
13. Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system.
- Author
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Nes, Johannes, Gessi, Marco, Sucker, Antje, Möller, Inga, Stiller, Mathias, Horn, Susanne, Scholz, Simone, Pischler, Carina, Stadtler, Nadine, Schilling, Bastian, Zimmer, Lisa, Hillen, Uwe, Scolyer, Richard, Buckland, Michael, Lauriola, Libero, Pietsch, Torsten, Waha, Andreas, Schadendorf, Dirk, Murali, Rajmohan, and Griewank, Klaus
- Abstract
Melanocytic tumors originating in the central nervous system (MT-CNS) are rare tumors that generally have a favorable prognosis, however malignant tumors do occur. Pathogenetically MT-CNS are not well characterized. Similar to uveal melanoma and blue nevi, they frequently harbor activating GNAQ or GNA11 mutations. Rare NRAS mutations have also been reported. Other mutations have not yet been described. We analyzed 19 MT-CNS, 7 uveal melanomas and 19 cutaneous melanomas using a targeted next generation sequencing approach analyzing 29 genes known to be frequently mutated in other melanocytic tumors (in particular uveal and cutaneous melanomas). In concordance with previous studies, cutaneous melanoma samples showed frequent NRAS or BRAF mutations, as well as mutations in other genes (e.g. NF1, RAC1, PIK3CA, ARID1A). Metastasized uveal melanomas exhibited mutations in GNAQ, GNA11 and BAP1. In contrast, MT-CNS almost exclusively demonstrated mutations in GNAQ (71 %) or GNA11 (12 %). Interestingly both GNA11 mutations identified were detected in MT-CNS diagnosed as intermediate grade melanocytomas which also recurred. One of these recurrent cases also harbored an inactivating BAP1 mutation and was found to have lost one copy of chromosome 3. Our findings show that while MT-CNS do have GNAQ or GNA11 mutations, they rarely harbor other recurrent mutations found in uveal or cutaneous melanomas. Considering chromosome 3 and BAP1 loss are robust markers of poor prognosis in uveal melanoma, it will prove interesting to determine whether these genomic alterations are also of prognostic significance in MT-CNS. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
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