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  • Hofving, Tobias,1989Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology (author)

The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • Bioscientifica,2018

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/265618
  • https://gup.ub.gu.se/publication/265618URI
  • https://doi.org/10.1530/erc-17-0445DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 profiling 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.

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  • Arvidsson, Yvonne,1960Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xarvyv (author)
  • Almobarak, BilalGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xalmob (author)
  • Inge, LindaGothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology(Swepub:gu)xarvli (author)
  • Pfragner, R. (author)
  • Persson, Marta,1979Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xwinma (author)
  • Stenman, Göran,1953Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xsteng (author)
  • Kristiansson, Erik,1978Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences(Swepub:gu)xkrier (author)
  • Johanson, Viktor,1958Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xjovik (author)
  • Nilsson, Ola,1957Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xnilol (author)
  • Göteborgs universitetSahlgrenska Cancer Center (creator_code:org_t)

Related titles

  • In:Endocrine-Related Cancer: Bioscientifica25:3, s. 367-3801351-00881479-6821

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