title: Whole-exome characterization of pancreatic neuroendocrine tumor cell lines BON-1 and QGP-1.
abstract: The human BON-1 and QGP-1 cell lines are two frequently used models in pancreatic neuroendocrine tumor (PNET) research. Data on the whole-exome genetic constitution of these cell lines is largely lacking. This study presents, to our knowledge, the first whole-exome profile of the BON-1 and QGP-1 cell lines. Cell line identity was confirmed by short tandem repeat profiling. Using GTG-banding and a CytoSNP-12v2 Beadchip array, cell line ploidy and chromosomal alterations were determined in BON-1 and QGP-1. The exomes of both cell lines were sequenced on Ilumina's HiSeq next-generation sequencing (NGS) platform. Single-nucleotide variants (SNVs) and insertions and deletions (indels) were detected using the Genome Analysis ToolKit. SNVs were validated by Sanger sequencing. Ploidy of BON-1 and QGP-1 was 3 and 4 respectively, with long stretches of loss of heterozygosity across multiple chromosomes, which is associated with aggressive tumor behavior. In BON-1, 57 frameshift indels and 1725 possible protein-altering SNVs were identified in the NGS data. In the QGP-1 cell line, 56 frameshift indels and 1095 SNVs were identified. ATRX, a PNET-associated gene, was mutated in both cell lines, while mutation of TSC2 was detected in BON-1. A mutation in NRAS was detected in BON-1, while KRAS was mutated in QGP-1, implicating aberrations in the RAS pathway in both cell lines. Homozygous mutations in TP53 with possible loss of function were identified in both cell lines. Various MUC genes, implicated in cell signaling, lubrication and chemical barriers, which are frequently expressed in PNET tissue samples, showed homozygous protein-altering SNVs in the BON-1 and QGP-1 cell lines.
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium timon.vandamme@uantwerp.be.
authors.forename: Timon
authors.initials: T
authors.lastname: Vandamme
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Fadime
authors.initials: F
authors.lastname: Dogan
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Elvire
authors.initials: E
authors.lastname: Van Assche
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: Beyens
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Vandeweyer
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Herder
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.affiliation: Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
authors.forename: Ken
authors.initials: K
authors.lastname: Op de Beeck
mesh_terms: D000483:Alleles; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics; D059472:Exome / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D018358:Neuroendocrine Tumors / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011003:Ploidies; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D009711:Nucleotides
keywords: BON-1; PNET; QGP-1; SNP array; whole-exome sequencing