Genetic Ancestry Analysis Reveals Misclassification of Commonly Used Cancer Cell Lines

Abstract

Background: Given the scarcity of cell lines from underrepresented populations, it is imperative that genetic ancestry for these cell lines is characterized. Consequences of cell line mischaracterization include squandered resources and publication retractions. Methods: We calculated genetic ancestry proportions for 15 cell lines to assess the accuracy of previous race/ethnicity classification and determine previously unknown estimates. DNA was extracted from cell lines and genotyped for ancestry informative markers representing West African (WA), Native American (NA), and European (EUR) ancestry. Results: Of the cell lines tested, all previously classified as White/Caucasian were accurately described with mean EUR ancestry proportions of 97%. Cell lines previously classified as Black/African American were not always accurately described. For instance, the 22Rv1 prostate cancer cell line was recently found to carry mixed genetic ancestry using a much smaller panel of markers. However, our more comprehensive analysis determined the 22Rv1 cell line carries 99% EUR ancestry. Most notably, the E006AA-hT prostate cancer cell line, classified as African American, was found to carry 92% EUR ancestry. We also determined the MDA-MB-468 breast cancer cell line carries 23% NA ancestry, suggesting possible Afro-Hispanic/ Latina ancestry. Conclusions: Our results suggest predominantly EUR ancestry for the White/Caucasian-designated cell lines, yet high variance in ancestry for the Black/African Americandesignated cell lines. In addition, we revealed an extreme misclassification of the E006AA-hT cell line. Impact: Genetic ancestry estimates offer more sophisticated characterization leading to better contextualization of findings. Ancestry estimates should be provided for all cell lines to avoid erroneous conclusions in disparities literature.

Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity

“…This expression pattern was recapitulative in PCa RC77 T/E cells when compared to their matched normal RC77 N/E cells. Recently identified renal cell carcinoma E006AA/hT cells [ 20 ] were used as a control for TMTC4 expression. In human tissues, TMTC4 protein expression was able to differentiate between PCa and BPH with high sensitivity and specificity.…”

Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition

“…Interestingly, co-culture of PC-3-or DU145-derived exosomes with either C4-2B, LNCaP, RC77T/E and E006AA cells promotes cell proliferation, migration and invasion capacities. Although a recent study reported that E006AA-hT cells are not African American PCa cells and, instead, they have 92% similarity to European ancestry and are 86% similar to renal cell carcinoma [32], these cells were used as a control recipient cells because they have low ITGA2 expression on cellular and exosomal levels. COS-1 and CV1 cells are kidney cells used as controls in a number of PCa studies [33,34].…”

“…CWR-R1ca cells were purchased from Millipore Sigma (Burlington, MA, USA). E006AA cells are also available from Millipore Sigma but recent report revealed that E006AA-hT were 86% closer to renal cell carcinoma [32]. These cells were cultured as we previously described [57].…”

Role of CYP3A5 in Modulating Androgen Receptor Signaling and Its Relevance to African American Men with Prostate Cancer

“…The three cell lines from AA origin, carry *1/*3 heterozygous wild type/mutant CYP3A5. E006aahT has been found to be not of African American origin [21] and carries *3/*3 homozygous mutation. We used LNCaP (*3/*3) and MDAPCa2b (*1/*3) cells for our current study as they are of NHWA and AA origin, respectively, and are AR positive commercially available (ATCC) and show similar response to androgens.…”