BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through 
Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a 
valuable biomaterial for cell biology research and a renewable source of DNA. 
While LCLs have been used extensively in cellular and genetic studies, the 
process of cell transformation and expansion during culturing may introduce 
genomic changes that may impact their use and the interpretation of subsequent 
genetic findings.
RESULTS: We performed whole exome sequencing on a tetrad family using DNA 
derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each 
individual. We generated over 4.7 GB of mappable sequence to a 125X read 
coverage per sample. An average of 19,354 genetic variants were identified. 
Comparison of the two DNA sources from each individual showed an average 
concordance rate of 95.69%. By lowering the variant calling parameters, the 
concordance rate between the paired samples increased to 99.82%. Sanger 
sequencing of a subset of the remaining discordant variants did confirm the 
presence of de novo mutations arising in LCLs.
CONCLUSIONS: By varying software stringency parameters, we identified 99% 
concordance between DNA sequences derived from the two different sources from 
the same donors. These results suggest that LCLs are an appropriate 
representation of the genetic material of the donor and suggest that EBV 
transformation can result in low-level generation of de novo mutations. 
Therefore, use of PBMC or early passage EBV-transformed cells is recommended. 
These findings have broad-reaching implications, as there are thousands of LCLs 
in public biorepositories and individual laboratories.