scholarly journals HGG-28. ONCOGENIC TYROSINE KINASE GENE FUSIONS IN SUPRATENTORIAL HIGH GRADE GLIOMAS OF YOUNG CHILDREN - COMPARISON OF RNA- AND DNA-BASED METHODS FOR THEIR RELIABLE DETECTION

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i23-i23
Author(s):  
Torsten Pietsch ◽  
Gerrit Gielen ◽  
Andreas Waha ◽  
Evelyn Doerner ◽  
Andre O von Bueren ◽  
...  
Keyword(s):  
Young Children ◽  
Tyrosine Kinase ◽  
Rna Sequencing ◽  
First Year ◽  
High Grade ◽  
Gene Fusions ◽  
Kinase Gene ◽  
Tyrosine Kinase Gene ◽  
First Year Of Life ◽  
Rna And Dna

Abstract High-grade diffuse gliomas in early childhood are characterized by a more favorable outcome compared to older children. We have shown in previous studies that these tumors are characterized by stable genomes. The occurrence of tyrosine kinase gene fusions in high-grade gliomas of infancy may represent therapeutic targets. 50 glioblastomas (GBM) with supratentorial location occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, Bonn University. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified on the DNA level by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET and Molecular Inversion Probe (MIP) methodology. On the RNA level, fusion transcripts were detected by targeted RNA sequencing as well as Nanostring assay with fusion-specific probes. 37 supratentorial GBM occurred in the first year of life, 13 GBM between one and four years. 18 cases showed fusions of ALK to different partners; all occurred in the first year of life (18/37, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two cases novel fusions. The different methods led to comparable results. Only recurrent fusions with known fusion partners were detectable with fusion sequence-specific Nanostring probes and library construction for targeted RNA sequencing failed in a fraction of cases. Break-apart FISH led to reliable results on the next day, and MIP technology represented the most sensitive method for analysis of FFPE samples. Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of glioblastomas of young children; most frequent were ALK fusions occurring in infant GBM. DNA-based MIP technology represented the most robust and sensitive assay. A combination of RNA- and DNA-based methods to detect these fusions with high reliability is recommended.

scholarly journals HGG-34. DETECTION OF ONCOGENIC FUSION EVENTS IN SUPRATENTORIAL GLIOBLASTOMAS OF YOUNG CHILDREN

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii349-iii350
Author(s):  
Torsten Pietsch ◽  
Christian Vokuhl ◽  
Gerrit H Gielen ◽  
Andre O von Bueren ◽  
Everlyn Dörner ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Rna Sequencing ◽  
First Year ◽  
Gene Fusions ◽  
Older Children ◽  
Kinase Gene ◽  
Dna And Rna ◽  
Infancy And Early Childhood ◽  
Stable Genome ◽  
First Year Of Life

Abstract INTRODUCTION Glioblastoma in infancy and early childhood is characterized by a more favorable outcome compared to older children, a stable genome, and the occurrence of tyrosine kinase gene fusions that may represent therapeutic targets. METHODS 50 glioblastomas (GBM) with supratentorial location occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, University of Bonn. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET, Molecular Inversion Probe (MIP) methodology, and targeted RNA sequencing. RESULTS 37 supratentorial GBM occurred in the first year of life, 13 GBM between one and four years. 18 cases showed fusions of ALK to different fusion partners; all occurred in the first year of life (18/37 cases, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two novel fusions. The different methods led to comparable results; targeted RNA sequencing was not successful in a fraction of cases. Break-apart FISH led to reliable results on the next day, MIP technology represented the most sensitive method for analysis of FFPE samples. CONCLUSIONS Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of glioblastomas of children younger than four years; the most frequent were ALK fusions occurring in infant GBM. DNA based MIP technology represented the most robust and sensitive assay.

Abstract LB-216: Frequent oncogenic tyrosine kinase gene fusions in supratentorial glioblastomas of young children

2020 ◽  
Author(s):  
Torsten Pietsch ◽  
Christian Vokuhl ◽  
Gerrit H. Gielen ◽  
Andre O. von Bueren ◽  
Evelyn Dörner ◽  
...  
Keyword(s):  
Young Children ◽  
Tyrosine Kinase ◽  
Gene Fusions ◽  
Kinase Gene ◽  
Tyrosine Kinase Gene

Abstract 894: Targeting ROS1 receptor tyrosine kinase gene fusions in non-small cell lung cancer

2012 ◽  
Author(s):  
Kurtis D. Davies ◽  
Anh T. Le ◽  
Margaret C. Skokan ◽  
Mariana F. Theodoro ◽  
Marileila Varella-Garcia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Small Cell ◽  
Gene Fusions ◽  
Small Cell Lung ◽  
Kinase Gene ◽  
Tyrosine Kinase Gene ◽  
Receptor Tyrosine Kinase Gene

scholarly journals Young children with Noonan syndrome: evaluation of feeding problems

2020 ◽  
Vol 179 (11) ◽  
pp. 1683-1688
Author(s):  
Jos M. T. Draaisma ◽  
Joris Drossaers ◽  
Lenie van den Engel-Hoek ◽  
Erika Leenders ◽  
Joyce Geelen
Keyword(s):  
Young Children ◽  
Noonan Syndrome ◽  
Early Onset ◽  
Late Onset ◽  
Tube Feeding ◽  
Genetic Mutation ◽  
First Year ◽  
Feeding Problems ◽  
Genetic Syndrome ◽  
First Year Of Life

Abstract Noonan syndrome (NS) is a common genetic syndrome with a high variety in phenotype. Even though genetic testing is possible, NS is still a clinical diagnosis. Feeding problems are often present in infancy. We investigated the feeding status of 108 patients with clinically and genetically confirmed NS. Only patients with a documented feeding status before the age of 6 were included. A distinction was made between patients with early onset feeding problems (< 1 year) and children with late onset feeding problems (> 1 year). Seventy-one of 108 patients had feeding problems, of which 40 patients required tube feeding. Children with a genetic mutation other than PTPN11 and SOS1 had significantly more feeding problems in the first year. Fifty-two of all 108 patients experienced early onset feeding problems, of which 33 required tube feeding. A strong decrease in prevalence of feeding problems was found after the first year of life. Fifteen children developed feeding problems later in life, of which 7 required tube feeding. Conclusion: Feeding problems occur frequently in children with NS, especially in children with NS based on genetic mutations other than PTPN11 and SOS1. Feeding problems develop most often in infancy and decrease with age. What is Known:• Young children with Noonan syndrome may have transient feeding problems.• Most of them will need tube feeding. What is New:• This is the first study of feeding problems in patients with clinically and genetically proven Noonan syndrome.• Feeding problems most often develop in infancy and resolve between the age of 1 and 2.

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