4 results on '"Triantafyllia Brozou"'
Search Results
2. Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia
- Author
-
Danielle Brandes, Layal Yasin, Karin Nebral, Jana Ebler, Dagmar Schinnerl, Daniel Picard, Anke K. Bergmann, Jubayer Alam, Stefan Köhrer, Oskar A. Haas, Andishe Attarbaschi, Tobias Marschall, Martin Stanulla, Arndt Borkhardt, Triantafyllia Brozou, Ute Fischer, and Rabea Wagener more...
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The mutational landscape of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common pediatric cancer, is not fully described partially because commonly applied short-read next generation sequencing has a limited ability to identify structural variations. By combining comprehensive analysis of structural variants (SVs), single-nucleotide variants (SNVs), and small insertions-deletions, new subtype-defining and therapeutic targets may be detected. We analyzed the landscape of somatic alterations in 60 pediatric patients diagnosed with the most common BCP-ALL subtypes, ETV6::RUNX1+ and classical hyperdiploid (HD), using conventional cytogenetics, single nucleotide polymorphism (SNP) array, whole exome sequencing (WES), and the novel optical genome mapping (OGM) technique. Ninety-five percent of SVs detected by cytogenetics and SNP-array were verified by OGM. OGM detected an additional 677 SVs not identified using the conventional methods, including (subclonal) IKZF1 deletions. Based on OGM, ETV6::RUNX1+ BCP-ALL harbored 2.7 times more SVs than HD BCP-ALL, mainly focal deletions. Besides SVs in known leukemia development genes (ETV6, PAX5, BTG1, CDKN2A), we identified 19 novel recurrently altered regions (in n ≥ 3) including 9p21.3 (FOCAD/HACD4), 8p11.21 (IKBKB), 1p34.3 (ZMYM1), 4q24 (MANBA), 8p23.1 (MSRA), and 10p14 (SFMBT2), as well as ETV6::RUNX1+ subtype-specific SVs (12p13.1 (GPRC5A), 12q24.21 (MED13L), 18q11.2 (MIB1), 20q11.22 (NCOA6)). We detected 3 novel fusion genes (SFMBT2::DGKD, PDS5B::STAG2, and TDRD5::LPCAT2), for which the sequence and expression were validated by long-read and whole transcriptome sequencing, respectively. OGM and WES identified double hits of SVs and SNVs (ETV6, BTG1, STAG2, MANBA, TBL1XR1, NSD2) in the same patient demonstrating the power of the combined approach to define the landscape of genomic alterations in BCP-ALL. more...
- Published
- 2023
- Full Text
- View/download PDF
Catalog
3. Resolving inherited and de novo germline predisposing sequence variants by means of whole exome trio analyses in childhood hematological malignancies
- Author
-
Triantafyllia Brozou, Layal Yasin, Danielle Brandes, Daniel Picard, Carolin Walter, Julian Varghese, Martin Dugas, Ute Fischer, Arndt Borkhardt, and Oskar A. Haas
- Subjects
pediatric hematological malignancies ,trio-whole-exome sequencing ,cancer predisposition syndrome ,inheritance pattern ,de novo mutations ,Pediatrics ,RJ1-570 - 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. more...
- Published
- 2023
- Full Text
- View/download PDF
4. Second-look surgery after pediatric brain tumor resection – Single center analysis of morbidity and volumetric efficacy
- Author
-
Ann Kristin Schmitz, Christopher Munoz-Bendix, Marc Remke, Triantafyllia Brozou, Arndt Borkhardt, Daniel Hänggi, and Thomas Beez
- Subjects
Children ,Neuro-oncology ,Residual tumor ,Volumetric analysis ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Introduction: Postoperative residual tumor can occur for intentional or unintentional reasons. Decision-making regarding second-look surgery has to weigh molecular biology, probability of total resection and prognostic relevance against potential additional morbidity. In interdisciplinary tumor boards the neurosurgeon has to estimate risk and efficacy of second-look surgery in individual cases, based on precise data. Research question: Aim of this study was to provide such data by analyzing morbidity and volumetric efficacy of second-look surgery at a designated pediatric neuro-oncology unit. Material and methods: Children who received second-look surgery in 2007–2018 after incomplete resections were analyzed retrospectively. Measurements were performed on early postoperative magnetic resonance imaging, comparing axial diameter-based measurement as well as computer-assisted volumetric analysis. Results: 59 patients (37% of the overall cohort; 21 female; mean age: 8 ± 5 years) received a subtotal (n = 35) or near total (n = 24) resection. After interdisciplinary case review, 12 of these patients received second-look surgery mainly for residual ependymoma. This led to further tumor volume reduction in all cases (new degrees of resection: subtotal = 2, near total = 6, gross total = 4). No new permanent morbidity or perioperative mortality was observed. Discussion and conclusion: Second-look surgery did not increase mortality and permanent morbidity, had an 8% rate of transient morbidity and achieved tumor volume reduction above 95% in 75% of selected cases, with 4 additional gross total resections. Second-look surgery is safe and effective with regard to volumetric outcome parameters even in cases with good initial resections, although the role of second-look surgery regarding oncological outcome has to be further investigated in times of personalized molecular medicine. more...
- Published
- 2022
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.