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Novel TPR::ROS1 Fus...
Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma.
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- Deland, Lily (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine,Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Keane, Simon, 1991 (author)
- Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Translationell medicin TRIM, Translational Medicine
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- Bontell, Thomas Olsson (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden ; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Fagman, Henrik, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Centrum för Cancerforskning (SCCR),Department of Laboratory Medicine,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden ; Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
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- Sjögren, Helene (author)
- Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden
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- Lind, Anders E (author)
- Gothenburg University,Göteborgs universitet,Core Facilities,Clinical Genomics Gothenburg, SciLife Labs, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Caren, Helena (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR),Sahlgrenska Center for Cancer Research, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Tisell, Magnus, 1964 (author)
- Department of Clinical Neuroscience and Rehabilitation, Sahlgrenska University Hospital, Gothenburg, Sweden
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- Nilsson, Jonas A (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR),Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Ejeskär, Katarina, 1969 (author)
- Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Translationell medicin TRIM, Translational Medicine
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- Sabel, Magnus, 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics,Childhood Cancer Centre, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden ; Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Abel, Frida, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine,Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden
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(creator_code:org_t)
- 2022-10-31
- 2022
- English.
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In: Cancer genomics & proteomics. - : Anticancer Research USA Inc.. - 1109-6535 .- 1790-6245. ; 19:6, s. 711-726
- Related links:
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https://doi.org/10.2...
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https://his.diva-por... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.2...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Although fusion genes involving the proto-oncogene receptor tyrosine kinase ROS1 are rare in pediatric glioma, targeted therapies with small inhibitors are increasingly being approved for histology-agnostic fusion-positive solid tumors.Here, we present a 16-month-old boy, with a brain tumor in the third ventricle. The patient underwent complete resection but relapsed two years after diagnosis and underwent a second operation. The tumor was initially classified as a low-grade glioma (WHO grade 2); however, methylation profiling suggested the newly WHO-recognized type: infant-type hemispheric glioma. To further refine the molecular background, and search for druggable targets, whole genome (WGS) and whole transcriptome (RNA-Seq) sequencing was performed.Concomitant WGS and RNA-Seq analysis revealed several segmental gains and losses resulting in complex structural rearrangements and fusion genes. Among the top-candidates was a novel TPR::ROS1 fusion, for which only the 3' end of ROS1 was expressed in tumor tissue, indicating that wild type ROS1 is not normally expressed in the tissue of origin. Functional analysis by Western blot on protein lysates from transiently transfected HEK293 cells showed the TPR::ROS1 fusion gene to activate the MAPK-, PI3K- and JAK/STAT- pathways through increased phosphorylation of ERK, AKT, STAT and S6. The downstream pathway activation was also confirmed by immunohistochemistry on tumor tissue slides from the patient.We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Humans
- Infant
- Male
- Gene Rearrangement
- Glioma
- genetics
- pathology
- HEK293 Cells
- Lung Neoplasms
- pathology
- Oncogene Proteins
- Fusion
- genetics
- Phosphatidylinositol 3-Kinases
- genetics
- Protein-Tyrosine Kinases
- genetics
- metabolism
- Proto-Oncogene Proteins
- genetics
- childhood cancer
- Translationell medicin TRIM
Publication and Content Type
- ref (subject category)
- art (subject category)
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Deland, Lily
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Keane, Simon, 19 ...
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Bontell, Thomas ...
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Fagman, Henrik, ...
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Sjögren, Helene
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Lind, Anders E
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Caren, Helena
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Tisell, Magnus, ...
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Nilsson, Jonas A
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Ejeskär, Katarin ...
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Sabel, Magnus, 1 ...
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Abel, Frida, 197 ...
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and Basic Medicine
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Cancer genomics ...
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University of Gothenburg
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University of Skövde