Whole-exome sequencing of LNCaP prostate cancer cell line
BACKGROUND. The LNCaP cell line is widely used as a model for prostate cancer. However, information on protein-changing mutations, genetic heterogeneity and genetic (in)stability is largely lacking for these cells. METHODS. Next-generation sequencing of the LNCaP exome revealed many single nucleotide variants (SNVs). To help identify the mutations that are most likely drivers of the oncogenic process, we developed an in silico protocol, which can be adapted for other exome analyses. RESULTS. We detected 1,802 non-synonymous SNVs and 218 small insertions and deletions in the LNCaP exome. We confirm the known mutations in the androgen receptor and the PTEN gene, but most other mutations remained undescribed until now. The presence of 38 out of 42 SNVs was confirmed in monoclonal as well as in polyclonal LNCaP derivatives. Moreover, most variants were also detectable in LNCaP mRNA. CONCLUSIONS. We provide an extensive database of genetic variations in the protein-coding part of the genome of LNCaP cells, which should be taken into consideration when using LNCaP cells or its derivatives as models for prostate cancer. From the analysis of several LNCaP-derived cultures and clones, we can confirm that the cell line is heterozygous for a large number of variants and that both the variant and the wild-type allele can be simultaneously expressed as mRNA. The fact that the SNVs in the E-cadherin, CDK4, Notch1, and PlexinB1 genes are absent in some of the subclones strongly indicates a degree of genetic instability.