Genetic Ancestry Analysis Reveals Misclassification of Commonly Used Cancer Cell Lines

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 American–designated 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.

[1]  Sourav Roy,et al.  Glucocorticoids Induce Stress Oncoproteins Associated with Therapy-Resistance in African American and European American Prostate Cancer Cells , 2018, Scientific Reports.

[2]  Christopher J Kemp,et al.  Personalized Cancer Models for Target Discovery and Precision Medicine. , 2018, Trends in cancer.

[3]  Charles Wang,et al.  RNA sequencing reveals upregulation of a transcriptomic program associated with stemness in metastatic prostate cancer cells selected for taxane resistance , 2018, Oncotarget.

[4]  J. Carpten,et al.  Exogenous IL‐6 induces mRNA splice variant MBD2_v2 to promote stemness in TP53 wild‐type, African American PCa cells , 2018, Molecular oncology.

[5]  I. Rzepecka,et al.  Clinical importance of the EMSY gene expression and polymorphisms in ovarian cancer , 2018, Oncotarget.

[6]  J. Rhim,et al.  Hypoxia-induced exosome secretion promotes survival of African-American and Caucasian prostate cancer cells , 2018, Scientific Reports.

[7]  Sourav Roy,et al.  The 22Rv1 prostate cancer cell line carries mixed genetic ancestry: Implications for prostate cancer health disparities research using pre‐clinical models , 2017, The Prostate.

[8]  Winnie S. Liang,et al.  Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases , 2017, PLoS genetics.

[9]  A. Bird.  Genetic determinants of the epigenome in development and cancer. , 2017, Swiss medical weekly.

[10]  Baosen Zhou,et al.  Genetic variation at the microRNA binding site of CAV1 gene is associated with lung cancer susceptibility , 2017, Oncotarget.

[11]  D. A. Eisner.  Reproducibility of science: Fraud, impact factors and carelessness , 2017, Journal of molecular and cellular cardiology.

[12]  R. Kittles,et al.  Warfarin Pharmacogenomics in Diverse Populations , 2017, Pharmacotherapy.

[13]  R. Kittles,et al.  Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men , 2017, The Prostate.

[14]  H. Augustin,et al.  Models in Translational Oncology: A Public Resource Database for Preclinical Cancer Research. , 2017, Cancer research.

[15]  A. Jemal,et al.  Socioeconomic and Racial/Ethnic Disparities in Cancer Mortality, Incidence, and Survival in the United States, 1950–2014: Over Six Decades of Changing Patterns and Widening Inequalities , 2017, Journal of environmental and public health.

[16]  G. Dotto,et al.  Racial Differences in Cancer Susceptibility and Survival: More Than the Color of the Skin? , 2017, Trends in cancer.

[17]  R. Dahiya,et al.  Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians , 2016, Oncotarget.

[18]  T. Sanchez,et al.  Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins* , 2016, Molecular & Cellular Proteomics.

[19]  Diogo Meyer,et al.  Increasing The Genetic Admixture of Available Lines of Human Pluripotent Stem Cells , 2016, Scientific Reports.

[20]  Kassandra I. Alcaraz,et al.  Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities , 2016, CA: a cancer journal for clinicians.

[21]  D. Allison,et al.  The Genetic Contribution of West-African Ancestry to Protection against Central Obesity in African-American Men but Not Women: Results from the ARIC and MESA Studies , 2016, Front. Genet..

[22]  S. Paik,et al.  Cancer Cell Line Panels Empower Genomics-Based Discovery of Precision Cancer Medicine , 2015, Yonsei medical journal.

[23]  Jiaoti Huang,et al.  Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells , 2015, Oncotarget.

[24]  R. Kittles,et al.  Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans: an analysis of a randomized controlled trial , 2015, Pharmacogenetics and genomics.

[25]  R. Neve,et al.  Reproducibility: changing the policies and culture of cell line authentication , 2015, Nature Methods.

[26]  Miguel Ángel Martínez,et al.  Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients , 2015, BMC Cancer.

[27]  D. Saunders,et al.  Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives , 2015, Genes to cells : devoted to molecular & cellular mechanisms.

[28]  R. Kittles,et al.  Association of Genetic Ancestry with Breast Cancer in Ethnically Diverse Women from Chicago , 2014, PLoS ONE.

[29]  Carson C Chow,et al.  Second-generation PLINK: rising to the challenge of larger and richer datasets , 2014, GigaScience.

[30]  T. Albrecht,et al.  Unexpected Findings in the Exploration of African American Underrepresentation in Biospecimen Collection and Biobanks , 2014, Journal of Cancer Education.

[31]  C. Ragin,et al.  Biospecimens, biobanking and global cancer research collaborations , 2014, Ecancermedicalscience.

[32]  S. Willard,et al.  Establishment and Characterization of a Highly Tumorigenic African American Prostate Cancer Cell Line, E006AA-hT , 2014, International journal of biological sciences.

[33]  B. Ring,et al.  Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review , 2014, PloS one.

[34]  J N Douglas,et al.  Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans , 2013, The Pharmacogenomics Journal.

[35]  R. Kittles,et al.  An anthropological genetic perspective on Creolization in the Anglophone Caribbean. , 2013, American journal of physical anthropology.

[36]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[37]  Christopher R. Gignoux,et al.  History Shaped the Geographic Distribution of Genomic Admixture on the Island of Puerto Rico , 2011, PloS one.

[38]  J. Rhim,et al.  Establishment and characterization of a pair of non-malignant and malignant tumor derived cell lines from an African American prostate cancer patient. , 2010, International journal of oncology.

[39]  D. Altshuler,et al.  A map of human genome variation from population-scale sequencing , 2010, Nature.

[40]  J. Eberwine,et al.  Mammalian cell transfection: the present and the future , 2010, Analytical and bioanalytical chemistry.

[41]  T. Pemberton,et al.  Lack of population diversity in commonly used human embryonic stem-cell lines. , 2010, The New England journal of medicine.

[42]  D. Absher,et al.  Characterizing the admixed African ancestry of African Americans , 2009, Genome Biology.

[43]  M. Stein,et al.  Measurement of admixture proportions and description of admixture structure in different U.S. populations , 2009, Human mutation.

[44]  Gabriel Silva,et al.  An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels , 2009, BMC Genetics.

[45]  M. Llano,et al.  Intensive RNAi with lentiviral vectors in mammalian cells. , 2009, Methods.

[46]  Gabriel Silva,et al.  Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America , 2009, Human mutation.

[47]  E. Ziv,et al.  Genetic ancestry and risk of breast cancer among U.S. Latinas. , 2008, Cancer research.

[48]  S. Tishkoff,et al.  African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. , 2008, Annual review of genomics and human genetics.

[49]  J. Brockmöller,et al.  Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment , 2008, European Journal of Clinical Pharmacology.

[50]  S. Lee.  Racializing drug design: implications of pharmacogenomics for health disparities. , 2005, American journal of public health.

[51]  Rui Mei,et al.  Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation , 2005, Human Genomics.

[52]  M. Stephens,et al.  Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. , 2003, Genetics.

[53]  Jonathan Scott Friedlaender,et al.  A Human Genome Diversity Cell Line Panel , 2002, Science.

[54]  W S Watkins,et al.  The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data. , 2000, American journal of human genetics.

[55]  S. Schwartz,et al.  A new human prostate carcinoma cell line, 22Rv1 , 1999, In Vitro Cellular & Developmental Biology - Animal.

[56]  M. Resnick,et al.  Xenografts of primary human prostatic carcinoma. , 1993, Journal of the National Cancer Institute.

[57]  C. Bj.  HeLa (for Henrietta Lacks). , 1974 .

[58]  L A Rogers,et al.  The American Type Culture Collection , 1925, Nature.

[59]  A. Jemal,et al.  Cancer statistics, 2018 , 2018, CA: a cancer journal for clinicians.

[60]  Shafiq A. Khan,et al.  TGF‐β Effects on Prostate Cancer Cell Migration and Invasion Require FosB , 2017, The Prostate.

[61]  Barney Cohen,et al.  Critical Perspectives on Racial and Ethnic Differences in Health in Late Life , 2004 .

[62]  B. C.,et al.  HeLa (for Henrietta Lacks). , 1974, Science.