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The neuroendocrine ...
The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines
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- Hofving, Tobias (författare)
- Göteborgs universitet,University of Gothenburg
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- Arvidsson, Yvonne, 1960 (författare)
- Göteborgs universitet,University of Gothenburg
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- Almobarak, Bilal (författare)
- Göteborgs universitet,University of Gothenburg
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- Inge, Linda (författare)
- Göteborgs universitet,University of Gothenburg
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- Pfragner, Roswitha (författare)
- Medizinische Universität Graz,Medical University of Graz
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- Persson, Marta (författare)
- Göteborgs universitet,University of Gothenburg
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- Stenman, Göran, 1953 (författare)
- Göteborgs universitet,University of Gothenburg
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- Kristiansson, Erik, 1978 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Johanson, Viktor (författare)
- Göteborgs universitet,University of Gothenburg
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- Nilsson, Ola, 1957 (författare)
- Göteborgs universitet,University of Gothenburg
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(creator_code:org_t)
- 2018
- 2018
- Engelska.
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Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 25:3, s. 367-380
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https://research.cha... (primary) (free)
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https://doi.org/10.1...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number rofiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Vorinostat
- Inhibitor screening
- GEPNET
- Cell lines
- Neuroendocrine tumour
- Trametinib
- Immunophenotyping
- Exome sequencing
- Copy number alterations
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Hofving, Tobias
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Arvidsson, Yvonn ...
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Almobarak, Bilal
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Inge, Linda
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Pfragner, Roswit ...
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Persson, Marta
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Stenman, Göran, ...
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Kristiansson, Er ...
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Johanson, Viktor
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Nilsson, Ola, 19 ...
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Cellbiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Immunologi inom ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
- Artiklar i publikationen
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Endocrine-Relate ...
- Av lärosätet
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Chalmers tekniska högskola