ena-STUDY-Universiteit Antwerpen-15-01-2015-14:26:13:850-97
Whole exome characterization of pancreatic neuroendocrine tumor cell lines BON-1 and QGP-1
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 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 CytoSNP-12v2 Beadchip array, cell line ploidy and chromosomal alterations were determined in BON-1 and QGP-1. The exome of both cell lines was sequenced on Ilumina’s HiSeq next generation sequencing (NGS) platform. Single Nucleotide Variants (SNVs) and indels were called using the Genome Analysis ToolKit. SNVs were validated with 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 behaviour. In BON-1, 57 frameshift indels and 1725 possible protein-altering SNVs were called 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 TSC2 contained a mutation in BON-1. NRAS showed a mutation 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 line.
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 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 CytoSNP-12v2 Beadchip array, cell line ploidy and chromosomal alterations were determined in BON-1 and QGP-1. The exome of both cell lines was sequenced on Ilumina’s HiSeq next generation sequencing (NGS) platform. Single Nucleotide Variants (SNVs) and indels were called using the Genome Analysis ToolKit. SNVs were validated with 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 behaviour. In BON-1, 57 frameshift indels and 1725 possible protein-altering SNVs were called 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 TSC2 contained a mutation in BON-1. NRAS showed a mutation 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 line.