Search

Your search keyword '"Brozou, Triantafyllia"' showing total 38 results
Start Over Author "Brozou, Triantafyllia" Search Limiters Full Text
38 results on '"Brozou, Triantafyllia"'

1. ATM germ line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological malignancies

Author

Elitzur, Sarah, Shiloh, Ruth, Loeffen, Jan L. C., Pastorczak, Agata, Takagi, Masatoshi, Bomken, Simon, Baruchel, Andre, Lehrnbecher, Thomas, Tasian, Sarah K., Abla, Oussama, Arad-Cohen, Nira, Astigarraga, Itziar, Ben-Harosh, Miriam, Bodmer, Nicole, Brozou, Triantafyllia, Ceppi, Francesco, Chugaeva, Liliia, Dalla Pozza, Luciano, Ducassou, Stephane, Escherich, Gabriele, Farah, Roula, Gibson, Amber, Hasle, Henrik, Hoveyan, Julieta, Jacoby, Elad, Jazbec, Janez, Junk, Stefanie, Kolenova, Alexandra, Lazic, Jelena, Lo Nigro, Luca, Mahlaoui, Nizar, Miller, Lane, Papadakis, Vassilios, Pecheux, Lucie, Pillon, Marta, Sarouk, Ifat, Stary, Jan, Stiakaki, Eftichia, Strullu, Marion, Tran, Thai Hoa, Ussowicz, Marek, Verdu-Amoros, Jaime, Wakulinska, Anna, Zawitkowska, Joanna, Stoppa-Lyonnet, Dominique, Taylor, A. Malcolm, Shiloh, Yosef, Izraeli, Shai, Minard-Colin, Veronique, Schmiegelow, Kjeld, Nirel, Ronit, Attarbaschi, Andishe, and Borkhardt, Arndt

Published
2024
Full Text
View/download PDF

2. A clinical screening tool to detect genetic cancer predisposition in pediatric oncology shows high sensitivity but can miss a substantial percentage of affected children

Author

Friedrich, Ulrike A., Bienias, Marc, Zinke, Claudia, Prazenicova, Maria, Lohse, Judith, Jahn, Arne, Menzel, Maria, Langanke, Jonas, Walter, Carolin, Wagener, Rabea, Brozou, Triantafyllia, Varghese, Julian, Dugas, Martin, Erlacher, Miriam, Schröck, Evelin, Suttorp, Meinolf, Borkhardt, Arndt, Hauer, Julia, and Auer, Franziska

Published
2023
Full Text
View/download PDF

4. Constitutional Microsatellite Instability, Genotype, and Phenotype Correlations in Constitutional Mismatch Repair Deficiency

Author

Gallon, Richard, Phelps, Rachel, Hayes, Christine, Brugieres, Laurence, Guerrini-Rousseau, Léa, Colas, Chrystelle, Muleris, Martine, Ryan, Neil A.J., Evans, D. Gareth, Grice, Hannah, Jessop, Emily, Kunzemann-Martinez, Annabel, Marshall, Lilla, Schamschula, Esther, Oberhuber, Klaus, Azizi, Amedeo A., Baris Feldman, Hagit, Beilken, Andreas, Brauer, Nina, Brozou, Triantafyllia, Dahan, Karin, Demirsoy, Ugur, Florkin, Benoît, Foulkes, William, Januszkiewicz-Lewandowska, Danuta, Jones, Kristi J., Kratz, Christian P., Lobitz, Stephan, Meade, Julia, Nathrath, Michaela, Pander, Hans-Jürgen, Perne, Claudia, Ragab, Iman, Ripperger, Tim, Rosenbaum, Thorsten, Rueda, Daniel, Sarosiek, Tomasz, Sehested, Astrid, Spier, Isabel, Suerink, Manon, Zimmermann, Stefanie-Yvonne, Zschocke, Johannes, Borthwick, Gillian M., Wimmer, Katharina, Burn, John, Jackson, Michael S., and Santibanez-Koref, Mauro

Published
2023
Full Text
View/download PDF

5. Alpha/beta values in pediatric medulloblastoma: implications for tailored approaches in radiation oncology.

Author

Jazmati, Danny, Sohn, Dennis, Hörner-Rieber, Juliane, Qin, Nan, Bölke, Edwin, Haussmann, Jan, Schwarz, Rudolf, Niggemeier, Niklas David, Borkhardt, Arndt, Babor, Florian, Brozou, Triantafyllia, Felek, Melissa, Tamaskovics, Balint, Melchior, Patrick, Beez, Thomas, Timmermann, Beate, Remke, Marc, Corradini, Stefanie, Schulz, Rémi Till, and Preugschas, Ronja-Linda

Subjects
BRAIN cancer, DOSE fractionation, MEDICAL sciences, MEDULLOBLASTOMA, BRAIN tumors
Abstract

Background: Medulloblastoma is the most common malignant pediatric brain tumor, typically treated with normofractionated craniospinal irradiation (CSI) with an additional boost over about 6 weeks in children older than 3 years. This study investigates the sensitivity of pediatric medulloblastoma cell lines to different radiation fractionation schedules. While extensively studied in adult tumors, these ratios remain unknown in pediatric cases due to the rarity of the disease. Materials and methods: Five distinct medulloblastoma cell lines (ONS76, UW228-3, DAOY, D283, D425) were exposed to varying radiation doses and fractionation schemes. In addition, ONS76 and UW228-3 stably overexpressing MYC were analyzed. Alpha/beta values, representing fractionation sensitivity, were quantified using the linear-quadratic model of radiation survival. Results: The study unveiled elevated alpha/beta ratios across diverse medulloblastoma cell lines, with a weighted mean alpha/beta value of 11.01 Gy (CI: 5.23–16.79 Gy). Neither TP53 status nor the levels of MYC expression influenced fractionated radiosensitivity. Furthermore, differences in alpha/beta values cannot be correlated with molecular subgroups (p = 0.07) or radiosensitivity (SF2). Conclusion: These in vitro findings strongly recommend normofractionated or hyperfractionated radiotherapy for paediatric medulloblastoma cases due to consistently high alpha/beta values across subgroups. Conversely, hypofractionated radiotherapy is not advisable within a curative approach. This study presents significant potential by enabling the estimation of radiobiological fractionations and dose effects in young, vulnerable patients, highlighting its importance for advancing patient-specific therapeutic strategies. [ABSTRACT FROM AUTHOR]

Published
2025
Full Text
View/download PDF

8. ATMgerm line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological malignancies

Author

Elitzur, Sarah, Shiloh, Ruth, Loeffen, Jan L. C., Pastorczak, Agata, Takagi, Masatoshi, Bomken, Simon, Baruchel, Andre, Lehrnbecher, Thomas, Tasian, Sarah K., Abla, Oussama, Arad-Cohen, Nira, Astigarraga, Itziar, Ben-Harosh, Miriam, Bodmer, Nicole, Brozou, Triantafyllia, Ceppi, Francesco, Chugaeva, Liliia, Dalla Pozza, Luciano, Ducassou, Stephane, Escherich, Gabriele, Farah, Roula, Gibson, Amber, Hasle, Henrik, Hoveyan, Julieta, Jacoby, Elad, Jazbec, Janez, Junk, Stefanie, Kolenova, Alexandra, Lazic, Jelena, Lo Nigro, Luca, Mahlaoui, Nizar, Miller, Lane, Papadakis, Vassilios, Pecheux, Lucie, Pillon, Marta, Sarouk, Ifat, Stary, Jan, Stiakaki, Eftichia, Strullu, Marion, Tran, Thai Hoa, Ussowicz, Marek, Verdu-Amoros, Jaime, Wakulinska, Anna, Zawitkowska, Joanna, Stoppa-Lyonnet, Dominique, Taylor, A. Malcolm, Shiloh, Yosef, Izraeli, Shai, Minard-Colin, Veronique, Schmiegelow, Kjeld, Nirel, Ronit, Attarbaschi, Andishe, and Borkhardt, Arndt

Abstract

•The major cause of death in patients with ataxia-telangiectasia and hematological malignancies is treatment-related toxicity.•The germ line ATMpathogenic variant functional class is a robust outcome predictor, which can be applied to therapy stratification.

Published
2024
Full Text
View/download PDF

9. Hyperdiploid acute lymphoblastic leukemia in children with LZTR1 germline variants

Author

Zipper, Lisa, primary, Wagener, Rabea, additional, Fischer, Ute, additional, Hoffmann, Anna, additional, Yasin, Layal, additional, Brandes, Danielle, additional, Soura, Stavrieta, additional, Anwar, Ammarah, additional, Walter, Carolin, additional, Varghese, Julian, additional, Hauer, Julia, additional, Auer, Franziska, additional, Bhatia, Sanil, additional, Dugas, Martin, additional, Junk, Stefanie V., additional, Stanulla, Martin, additional, Haas, Oskar A., additional, Borkhardt, Arndt, additional, Reiff, Tobias, additional, and Brozou, Triantafyllia, additional

Published
2024
Full Text
View/download PDF

12. Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia

Author

Brandes, Danielle, primary, Yasin, Layal, additional, Nebral, Karin, additional, Ebler, Jana, additional, Schinnerl, Dagmar, additional, Picard, Daniel, additional, Bergmann, Anke K., additional, Alam, Jubayer, additional, Köhrer, Stefan, additional, Haas, Oskar A., additional, Attarbaschi, Andishe, additional, Marschall, Tobias, additional, Stanulla, Martin, additional, Borkhardt, Arndt, additional, Brozou, Triantafyllia, additional, Fischer, Ute, additional, and Wagener, Rabea, additional

Published
2023
Full Text
View/download PDF

14. Resolving inherited and de novo germline predisposing sequence variants by means of whole exome trio analyses in childhood hematological malignancies

Author

Brozou, Triantafyllia, Yasin, Layal, Brandes, Danielle, Picard, Daniel, Walter, Carolin, Varghese, Julian, Dugas, Martin, Fischer, Ute, Borkhardt, Arndt, and Haas, Oskar A.

Subjects
Pediatrics, Perinatology and Child Health
Abstract

Molecular screening tools have significantly eased the assessment of potential germline susceptibility factors that may underlie the development of pediatric malignancies. Most of the hitherto published studies utilize the comparative analyses of the respective patients' germline and tumor tissues for this purpose. Since this approach is not able to discriminate between de novo and inherited sequence variants, we performed whole exome trio analyses in a consecutive series of 131 children with various forms of hematologic malignancies and their parents. In total, we identified 458 de novo variants with a range from zero to 28 (median value = 3) per patient, although most of them (58%) had only up to three per exome. Overall, we identified bona fide cancer predisposing alterations in five of the investigated 131 (3.8%) patients. Three of them had de novo pathogenic lesions in the SOS1, PTPN11 and TP53 genes and two of them parentally inherited ones in the STK11 and PMS2 genes that are specific for a Peutz-Jeghers and a constitutional mismatch repair deficiency (CMMRD) syndrome, respectively. Notwithstanding that we did not identify a disease-specific alteration in the two cases with the highest number of de novo variants, one of them developed two almost synchronous malignancies: a myelodysplastic syndrome and successively within two months a cerebral astrocytoma. Moreover, we also found that the rate of de novo sequence variants in the offspring increased especially with the age of the father, but less so with that of the mother. We therefore conclude that trio analyses deliver an immediate overview about the inheritance pattern of the entire spectrum of sequence variants, which not only helps to securely identify the de novo or inherited nature of genuinely disease-related lesions, but also of all other less obvious variants that in one or the other way may eventually advance our understanding of the disease process.

Published
2023
Full Text
View/download PDF

16. Deciphering the Somatic and Germline Structural Variation Landscape in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia By Whole Genome Optical Mapping

Author

Brandes, Danielle, primary, Brozou, Triantafyllia, additional, Nebral, Karin, additional, Bergmann, Anke K., additional, Haas, Oskar A., additional, Köhrer, Stefan, additional, Stanulla, Martin, additional, Fischer, Ute, additional, Borkhardt, Arndt, additional, and Wagener, Rabea, additional

Published
2022
Full Text
View/download PDF

17. Recurrent Germline Variant in RAD21 Predisposes Children to Lymphoblastic Leukemia or Lymphoma

Author

Schedel, Anne, Friedrich, Ulrike Anne, Morcos, Mina N.F., Wagener, Rabea, Mehtonen, Juha, Watrin, Titus, Saitta, Claudia, Brozou, Triantafyllia, Michler, Pia, Walter, Carolin, Försti, Asta, Baksi, Arka, Menzel, Maria, Horak, Peter, Paramasivam, Nagarajan, Fazio, Grazia, Autry, Robert J., Fröhling, Stefan, Suttorp, Meinolf, Gertzen, Christoph, Gohlke, Holger, Bhatia, Sanil, Wadt, Karin, Schmiegelow, Kjeld, Dugas, Martin, Richter, Daniela, Glimm, Hanno, Heinäniemi, Merja, Jessberger, Rolf, Cazzaniga, Gianni, Borkhardt, Arndt, Hauer, Julia, Auer, Franziska, Schedel, Anne, Friedrich, Ulrike Anne, Morcos, Mina N.F., Wagener, Rabea, Mehtonen, Juha, Watrin, Titus, Saitta, Claudia, Brozou, Triantafyllia, Michler, Pia, Walter, Carolin, Försti, Asta, Baksi, Arka, Menzel, Maria, Horak, Peter, Paramasivam, Nagarajan, Fazio, Grazia, Autry, Robert J., Fröhling, Stefan, Suttorp, Meinolf, Gertzen, Christoph, Gohlke, Holger, Bhatia, Sanil, Wadt, Karin, Schmiegelow, Kjeld, Dugas, Martin, Richter, Daniela, Glimm, Hanno, Heinäniemi, Merja, Jessberger, Rolf, Cazzaniga, Gianni, Borkhardt, Arndt, Hauer, Julia, and Auer, Franziska

Abstract

Somatic loss of function mutations in cohesin genes are frequently associated with various cancer types, while cohesin disruption in the germline causes cohesinopathies such as Cornelia‐de‐ Lange syndrome (CdLS). Here, we present the discovery of a recurrent heterozygous RAD21 germline aberration at amino acid position 298 (p.P298S/A) identified in three children with lymphoblastic leukemia or lymphoma in a total dataset of 482 pediatric cancer patients. While RAD21 p.P298S/A did not disrupt the formation of the cohesin complex, it altered RAD21 gene expression, DNA damage response and primary patient fibroblasts showed increased G2/M arrest after irradiation and Mitomycin‐C treatment. Subsequent single‐cell RNA‐sequencing analysis of healthy human bone marrow confirmed the upregulation of distinct cohesin gene patterns during hematopoiesis, highlighting the importance of RAD21 expression within proliferating B‐ and T‐cells. Our clinical and functional data therefore suggest that RAD21 germline variants can predispose to childhood lymphoblastic leukemia or lymphoma without displaying a CdLS phenotype.

Published
2022

18. Recurrent Germline Variant in RAD21 Predisposes Children to Lymphoblastic Leukemia or Lymphoma

Author

Schedel, Anne, primary, Friedrich, Ulrike, additional, Morcos, Mina, additional, Wagener, Rabea, additional, Mehtonen, Juha, additional, Watrin, Titus, additional, Saitta, Claudia, additional, Brozou, Triantafyllia, additional, Michler, Pia, additional, Walter, Carolin, additional, Försti, Asta, additional, Baksi, Arka, additional, Menzel, Maria, additional, Horak, Peter, additional, Paramasivam, Nagarajan, additional, Fazio, Grazia, additional, Autry, Robert, additional, Fröhling, Stefan, additional, Suttorp, Meinolf, additional, Gertzen, Christoph, additional, Gohlke, Holger, additional, Bhatia, Sanil, additional, Wadt, Karin, additional, Schmiegelow, Kjeld, additional, Dugas, Martin, additional, Richter, Daniela, additional, Glimm, Hanno, additional, Heinäniemi, Merja, additional, Jessberger, Rolf, additional, Cazzaniga, Gianni, additional, Borkhardt, Arndt, additional, Hauer, Julia, additional, and Auer, Franziska, additional

Published
2022
Full Text
View/download PDF

19. Multimodal Treatment of Nasopharyngeal Carcinoma in Children, Adolescents and Young Adults-Extended Follow-Up of the NPC-2003-GPOH Study Cohort and Patients of the Interim Cohort

Author

Römer, Tristan, primary, Franzen, Sabrina, additional, Kravets, Hanna, additional, Farrag, Ahmed, additional, Makowska, Anna, additional, Christiansen, Hans, additional, Eble, Michael J., additional, Timmermann, Beate, additional, Staatz, Gundula, additional, Mottaghy, Felix M., additional, Bührlen, Martina, additional, Hagenah, Ulrich, additional, Puzik, Alexander, additional, Driever, Pablo Hernáiz, additional, Greiner, Jeanette, additional, Jorch, Norbert, additional, Tippelt, Stephan, additional, Schneider, Dominik T., additional, Kropshofer, Gabriele, additional, Overbeck, Tobias R., additional, Christiansen, Holger, additional, Brozou, Triantafyllia, additional, Escherich, Gabriele, additional, Becker, Martina, additional, Friesenbichler, Waltraud, additional, Feuchtinger, Tobias, additional, Puppe, Wolfram, additional, Heussen, Nicole, additional, Hilgers, Ralf D., additional, and Kontny, Udo, additional

Published
2022
Full Text
View/download PDF

20. Recurrent Germline Variant in the Cohesin Complex Gene RAD21 Predisposes Children to Lymphoblastic Leukemia and Lymphoma

Author

Schedel, Anne, primary, Friedrich, Ulrike Anne, additional, Wagener, Rabea, additional, Mehtonen, Juha, additional, Saitta, Claudia, additional, Brozou, Triantafyllia, additional, Michler, Pia, additional, Walter, Carolin, additional, Horak, Peter, additional, Paramasivam, Nagarajan, additional, Fazio, Grazia, additional, Fröhling, Stefan, additional, Dugas, Martin, additional, Richter, Daniela, additional, Glimm, Hanno, additional, Heinäniemi, Merja, additional, Jessberger, Rolf, additional, Cazzaniga, Giovanni, additional, Borkhardt, Arndt, additional, Hauer, Julia, additional, and Auer, Franziska, additional

Published
2021
Full Text
View/download PDF

22. Germline POT1 Deregulation Can Predispose to Myeloid Malignancies in Childhood

Author

Michler, Pia, primary, Schedel, Anne, additional, Witschas, Martha, additional, Friedrich, Ulrike Anne, additional, Wagener, Rabea, additional, Mehtonen, Juha, additional, Brozou, Triantafyllia, additional, Menzel, Maria, additional, Walter, Carolin, additional, Nabi, Dalileh, additional, Pearce, Glen, additional, Erlacher, Miriam, additional, Göhring, Gudrun, additional, Dugas, Martin, additional, Heinäniemi, Merja, additional, Borkhardt, Arndt, additional, Stölzel, Friedrich, additional, Hauer, Julia, additional, and Auer, Franziska, additional

Published
2021
Full Text
View/download PDF

24. ATM Germline Pathogenic Variants Affect Treatment Outcomes in Children with Acute Lymphoblastic Leukemia/Lymphoma and Ataxia Telangiectasia

Author

Elitzur, Sarah, Shiloh, Ruth, Loeffen, Jan, Pastorczak, Agata, Takagi, Masatoshi, Bomken, Simon, Baruchel, Andre, Ducassou, Stephane, Mahlaoui, Nizar, Strullu, Marion, Lehrnbecher, Thomas, Schmiegelow, Kjeld, Abla, Oussama, Anderzhanova, Liliia, Arad-Cohen, Nira, Astigarraga, Itziar, Ben-Harosh, Miriam, Ceppi, Francesco, Bodmer, Nicole, Brozou, Triantafyllia, Dalla-Pozza, Luciano, Escherich, Gabriele, Farah, Roula, Gibson, Amber, Hasle, Henrik, Hoveyan, Julieta, Jacoby, Elad, Jazbec, Janez, Kolenova, Alexandra, Lazic, Jelena, Lo Nigro, Luca, Miller, Lane, Papadakis, Vassilios, Pecheux, Lucie, Pillon, Marta, Sarouk, Ifat, Stary, Jan, Stiakaki, Eftichia, Tasian, Sarah K., Tran, Thai Hoa, Ussowicz, Marek, Verdu-Amoros, Jose Jaime, Wakulinska, Anna, Zawitkowska, Joanna, Stoppa-Lyonnet, Dominique, Taylor, Malcolm, Shiloh, Yosef, Izraeli, Shai, Nirel, Ronit, Minard-Colin, Veronique, Attarbaschi, Andishe, and Borkhardt, Arndt

Published
2023
Full Text
View/download PDF

25. Supratentorial ependymoma in childhood: more than just RELA or YAP

Author

Zschernack, Valentina, Junger, Stephanie T., Mynarek, Martin, Rutkowski, Stefan, Garre, Maria Luisa, Ebinger, Martin, Neu, Marie, Faber, Joerg, Erdlenbruch, Bernhard, Claviez, Alexander, Bielack, Stefan, Brozou, Triantafyllia, Fruehwald, Michael C., Doerner, Evelyn, Dreschmann, Verena, Stock, Annika, Solymosi, Laszlo, Hench, Juergen, Frank, Stephan, Vokuhl, Christian, Waha, Andreas, Andreiuolo, Felipe, Pietsch, Torsten, Zschernack, Valentina, Junger, Stephanie T., Mynarek, Martin, Rutkowski, Stefan, Garre, Maria Luisa, Ebinger, Martin, Neu, Marie, Faber, Joerg, Erdlenbruch, Bernhard, Claviez, Alexander, Bielack, Stefan, Brozou, Triantafyllia, Fruehwald, Michael C., Doerner, Evelyn, Dreschmann, Verena, Stock, Annika, Solymosi, Laszlo, Hench, Juergen, Frank, Stephan, Vokuhl, Christian, Waha, Andreas, Andreiuolo, Felipe, and Pietsch, Torsten

Abstract

Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a YAP-MAMLD1 fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-RELA/non-YAP supratentorial ependymomas that were systematically characterized by means of their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis of fusion transcripts by Nanostring technology, and RNA sequencing. Based upon histological and immunohistochemical features two main patterns were identified-RELA-like (n = 9) and tanycytic ependymomas (n = 6). In the RELA-like group histologically assigned to WHO grade III and resembling RELA-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-kappa B pathway. Three tumors showed alternative C11orf95 fusions to MAML2 or NCOA1. A methylation-based brain tumor classifier assigned two RELA-like tumors to the methylation class EP, RELA-fusion; the others demonstrated no significant similarity score. Of the tanycytic group, 5/6 tumors were assigned a WHO grade II. No gene fusions were detected. Methylation profiling did not show any association with an established methylation class. We additionally identified two astroblastoma-like tumors that both presented with chromothripsis of chromosome 22 but lacked MN1 breaks according to FISH analysis. They revealed novel fusion events involving genes in chromosome 22. One further tumor with polyploid cytogenetics was interpreted as PFB ependymoma by the brain tumor methylation classifier but had no relation to the posterior fossa. Clinical follow-up was available for 16/18 patients. Patients with tanycytic and astroblastoma-like tumors had no relapse, while 2 patie

Published
2021

26. QRICH1 variants in Ververi‐Brady syndrome—delineation of the genotypic and phenotypic spectrum

Author

Föhrenbach, Melanie, primary, Jamra, Rami Abou, additional, Borkhardt, Arndt, additional, Brozou, Triantafyllia, additional, Muschke, Petra, additional, Popp, Bernt, additional, Rey, Linda K., additional, Schaper, Jörg, additional, Surowy, Harald, additional, Zenker, Martin, additional, Zweier, Christiane, additional, Wieczorek, Dagmar, additional, and Redler, Silke, additional

Published
2020
Full Text
View/download PDF

27. Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment

Author

Hrusak, Ondrej, Kalina, Tomas, Wolf, Joshua, Balduzzi, Adriana, Provenzi, Massimo, Rizzari, Carmelo, Rives, Susana, del Pozo Carlavilla, María, Alonso, Maria E.V., Domínguez-Pinilla, Nerea, Bourquin, Jean Pierre, Schmiegelow, Kjeld, Attarbaschi, Andishe, Grillner, Pernilla, Mellgren, Karin, van der Werff ten Bosch, Jutte, Pieters, Rob, Brozou, Triantafyllia, Borkhardt, Arndt, Escherich, Gabriele, Lauten, Melchior, Stanulla, Martin, Smith, Owen, Yeoh, Allen E.J., Elitzur, Sarah, Vora, Ajay, Li, Chi Kong, Ariffin, Hany, Kolenova, Alexandra, Dallapozza, Luciano, Farah, Roula, Lazic, Jelena, Manabe, Atsushi, Styczynski, Jan, Kovacs, Gabor, Ottoffy, Gabor, Felice, Maria S., Buldini, Barbara, Conter, Valentino, Stary, Jan, Schrappe, Martin, Hrusak, Ondrej, Kalina, Tomas, Wolf, Joshua, Balduzzi, Adriana, Provenzi, Massimo, Rizzari, Carmelo, Rives, Susana, del Pozo Carlavilla, María, Alonso, Maria E.V., Domínguez-Pinilla, Nerea, Bourquin, Jean Pierre, Schmiegelow, Kjeld, Attarbaschi, Andishe, Grillner, Pernilla, Mellgren, Karin, van der Werff ten Bosch, Jutte, Pieters, Rob, Brozou, Triantafyllia, Borkhardt, Arndt, Escherich, Gabriele, Lauten, Melchior, Stanulla, Martin, Smith, Owen, Yeoh, Allen E.J., Elitzur, Sarah, Vora, Ajay, Li, Chi Kong, Ariffin, Hany, Kolenova, Alexandra, Dallapozza, Luciano, Farah, Roula, Lazic, Jelena, Manabe, Atsushi, Styczynski, Jan, Kovacs, Gabor, Ottoffy, Gabor, Felice, Maria S., Buldini, Barbara, Conter, Valentino, Stary, Jan, and Schrappe, Martin

Abstract

Introduction: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. Aim and methods: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. Results: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. Conclusion: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

Published
2020

30. QRICH1 variants in Ververi‐Brady syndrome—delineation of the genotypic and phenotypic spectrum.

Author

Föhrenbach, Melanie, Jamra, Rami Abou, Borkhardt, Arndt, Brozou, Triantafyllia, Muschke, Petra, Popp, Bernt, Rey, Linda K., Schaper, Jörg, Surowy, Harald, Zenker, Martin, Zweier, Christiane, Wieczorek, Dagmar, and Redler, Silke

Subjects
SHORT stature, FRAMESHIFT mutation, SYNDROMES, PHENOTYPES, MISSENSE mutation
Abstract

Ververi‐Brady syndrome (VBS, # 617982) is a rare developmental disorder, and loss‐of‐function variants in QRICH1 were implicated in its etiology. Furthermore, a recognizable phenotype was proposed comprising delayed speech, learning difficulties and dysmorphic signs. Here, we present four unrelated individuals with one known nonsense variant (c.1954C > T; p.[Arg652*]) and three novel de novo QRICH1 variants, respectively. These included two frameshift mutations (c.832_833del; p.(Ser278Leufs*25), c.1812_1813delTG; p.(Glu605Glyfs*25)) and interestingly one missense mutation (c.2207G > A; p.[Ser736Asn]), expanding the mutational spectrum. Enlargement of the cohort by these four individuals contributes to the delineation of the VBS phenotype and suggests expressive speech delay, moderate motor delay, learning difficulties/mild ID, mild microcephaly, short stature and notable social behavior deficits as clinical hallmarks. In addition, one patient presented with nephroblastoma. The possible involvement of QRICH1 in pediatric cancer assumes careful surveillance a key priority for outcome of these patients. Further research and enlargement of cohorts are warranted to learn about the genetic architecture and the phenotypic spectrum in more detail. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

33. Diagnostic challenges in a child with early onset desmoplastic medulloblastoma and homozygous variants in MSH2and MSH6

Author

Taeubner, Julia, Wimmer, Katharina, Muleris, Martine, Lascols, Olivier, Colas, Chrystelle, Fauth, Christine, Brozou, Triantafyllia, Felsberg, Joerg, Riemer, Jasmin, Gombert, Michael, Ginzel, Sebastian, Hoell, Jessica, Borkhardt, Arndt, and Kuhlen, Michaela

Abstract

Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer susceptibility syndrome caused by biallelic germline mutations in one of the mismatch repair (MMR) genes. The spectrum of CMMRD-associated tumours is very broad and many CMMRD patients additionally display signposting non-neoplastic features, most frequently café-au-lait macules and other pigmentation alterations. We report on a 13-month-old girl suspected of having CMMRD due to a desmoplastic medulloblastoma and a striking skin pigmentation that included multiple café-au-lait macules, hypopigmented areas and Mongolian spots. Whole-exome sequencing revealed homozygosity for MSH2variant p.(Leu92Val) and MSH6variant p.(Val809del), both variants of uncertain significance (VUS). Immunohistochemical analysis of the tumour tissue showed expression of all four MMR proteins and gMSI testing was negative. However, functional assays demonstrated that the cells of the patient displayed methylation tolerance and ex vivo microsatellite instability, which unequivocally confirmed the diagnosis of CMMRD. Taken together, the results render the MSH2variant unlikely to be responsible for the phenotype, while they are compatible with MSH6-associated CMMRD. This case illustrates the diagnostic strategy of confirming CMMRD syndrome in patients with VUS.

Published
2018
Full Text
View/download PDF

34. ATMGermline Pathogenic Variants Affect Treatment Outcomes in Children with Acute Lymphoblastic Leukemia/Lymphoma and Ataxia Telangiectasia

Author

Elitzur, Sarah, Shiloh, Ruth, Loeffen, Jan, Pastorczak, Agata, Takagi, Masatoshi, Bomken, Simon, Baruchel, Andre, Ducassou, Stephane, Mahlaoui, Nizar, Strullu, Marion, Lehrnbecher, Thomas, Schmiegelow, Kjeld, Abla, Oussama, Anderzhanova, Liliia, Arad-Cohen, Nira, Astigarraga, Itziar, Ben-Harosh, Miriam, Ceppi, Francesco, Bodmer, Nicole, Brozou, Triantafyllia, Dalla-Pozza, Luciano, Escherich, Gabriele, Farah, Roula, Gibson, Amber, Hasle, Henrik, Hoveyan, Julieta, Jacoby, Elad, Jazbec, Janez, Kolenova, Alexandra, Lazic, Jelena, Lo Nigro, Luca, Miller, Lane, Papadakis, Vassilios, Pecheux, Lucie, Pillon, Marta, Sarouk, Ifat, Stary, Jan, Stiakaki, Eftichia, Tasian, Sarah K., Tran, Thai Hoa, Ussowicz, Marek, Verdu-Amoros, Jose Jaime, Wakulinska, Anna, Zawitkowska, Joanna, Stoppa-Lyonnet, Dominique, Taylor, Malcolm, Shiloh, Yosef, Izraeli, Shai, Nirel, Ronit, Minard-Colin, Veronique, Attarbaschi, Andishe, and Borkhardt, Arndt

Abstract

IntroductionAtaxia telangiectasia (A-T) is a multisystem disorder caused by biallelic germline pathogenic variants (PV) in the ATM gene. An important feature of A-T is an increased predisposition to cancer with a reported incidence of 25%, primarily attributed to hematological malignancies. Patients with A-T and cancer are usually excluded from therapeutic clinical trials, limited information thus exists concerning their treatment outcomes and toxicity profiles and consequently, optimal management strategies are unclear and an unmet need. In this multinational study, we aimed to investigate the characteristics and outcomes of leukemia and lymphoma in a large cohort of children with A-T and to determine risk factors which impact treatment outcome in order to generate consensus and data-based prospective treatment recommendations.

Published
2023
Full Text
View/download PDF

37. Novel Germline POT1Variant Predisposes to Childhood Acute Myeloid Leukemia

Author

Michler, Pia, Auer, Franziska, Wagener, Rabea, Brozou, Triantafyllia, Friedrich, Ulrike Anne, Walter, Carolin, Dugas, Martin, Borkhardt, Arndt, Stölzel, Friedrich, and Hauer, Julia

Abstract

Introduction:Current studies indicate a contribution of germline predisposition in the development of approximately 8.5% of childhood cancers (Zhang J. et al., N Engl J Med, 2015), although their apparent rate is estimated to be much higher. Understanding tumor evolution based on a predisposed cell can open unknown doors for prevention and therapy of childhood cancer e.g., leukemia. Here we present a novel rare (MAF<0.1%) germline POT1variant (Q199*) predisposing to acute myeloid leukemia (AML). POT1 as part of the telomeric shelterin complex is known to play an important role in DNA damage protection, telomere length maintenance and chromosomal stability (Calvete O. et al., Nat. Commun., 2015). POT1variants are associated with a broad range of cancer, including myeloid and lymphoid neoplasms in adults (Lim T.L. et al., Leukemia, 2021), but not yet described for myeloid malignancies in childhood.

Published
2021
Full Text
View/download PDF

38. Recurrent Germline Variant in the Cohesin Complex Gene RAD21Predisposes Children to Lymphoblastic Leukemia and Lymphoma

Author

Schedel, Anne, Friedrich, Ulrike Anne, Wagener, Rabea, Mehtonen, Juha, Saitta, Claudia, Brozou, Triantafyllia, Michler, Pia, Walter, Carolin, Horak, Peter, Paramasivam, Nagarajan, Fazio, Grazia, Fröhling, Stefan, Dugas, Martin, Richter, Daniela, Glimm, Hanno, Heinäniemi, Merja, Jessberger, Rolf, Cazzaniga, Giovanni, Borkhardt, Arndt, Hauer, Julia, and Auer, Franziska

Abstract

Introduction:Cohesin complex genes are commonly mutated in cancer particularly in myeloid malignancies. Yet patients with germline mutations in cohesin genes, leading to cohesinopathies like Cornelia-de-Lange syndrome (CdLS) are generally not known to be tumor-prone. The complex plays a major role in chromosome alignment and segregation (Uhlmann, Nature Reviews Molecular Cell Biology, 2016),homologous recombination-driven DNA repair (Ström et al., Molecular Cell, 2004) and regulation of gene expression (Busslinger et al., Nature, 2017). To deepen the understanding of cohesin variants in cancer predisposition, we performed TRIO Sequencing in two independent pediatric cancer cohorts. Thereby, we identified a novel recurrent heterozygous germline variant in the cohesin gene RAD21not described in CdLS patients ,located in the binding domain of the cofactors WAPL and PDS5B .

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results