The 22Rv1 prostate cancer cell line carries mixed genetic ancestry: Implications for prostate cancer health disparities research using pre‐clinical models

Abstract

BACKGROUND Understanding how biological factors contribute to prostate cancer (PCa) health disparities requires mechanistic functional analysis of specific genes or pathways in pre-clinical cellular and animal models of this malignancy. The 22Rv1 human prostatic carcinoma cell line was originally derived from the parental CWR22R cell line. Although 22Rv1 has been well characterized and used in numerous mechanistic studies, no racial identifier has ever been disclosed for this cell line. In accordance with the need for racial diversity in cancer biospecimens and recent guidelines by the NIH on authentication of key biological resources, we sought to determine the ancestry of 22RV1 and authenticate previously reported racial identifications for four other PCa cell lines. METHODS We used 29 established Ancestry Informative Marker (AIM) single nucleotide polymorphisms (SNPs) to conduct DNA ancestry analysis and assign ancestral proportions to a panel of five PCa cell lines that included 22Rv1, PC3, DU145, MDA-PCa-2b, and RC-77T/E. RESULTS We found that 22Rv1 carries mixed genetic ancestry. The main ancestry proportions for this cell line were 0.41 West African (AFR) and 0.42 European (EUR). In addition, we verified the previously reported racial identifications for PC3 (0.73 EUR), DU145 (0.63 EUR), MDA-PCa-2b (0.73 AFR), and RC-77T/E (0.74 AFR) cell lines. CONCLUSIONS Considering the mortality disparities associated with PCa, which disproportionately affect African American men, there remains a burden on the scientific community to diversify the availability of biospecimens, including cell lines, for mechanistic studies on potential biological mediators of these disparities. This study is beneficial by identifying another PCa cell line that carries substantial AFR ancestry. This finding may also open the door to new perspectives on previously published studies using this cell line.

Ancestral characterization of 1018 cancer cell lines highlights disparities and reveals gene expression and mutational differences

“…Prostate cancer cell lines are notable for having entirely European ancestry in our data set, despite prostate cancer being the most common cancer among all men and having an estimated incidence rate that is 70% higher among men of African ancestry than it is among men of European ancestry . This is concordant with recent results from Woods‐Burnham and colleagues, who identified substantial African ancestry in a commercially available prostate cancer cell line with previously unknown ancestry, and noted the lack of racial diversity in commercially available prostate cancer cell lines . In esophageal cancer, which is less common among males of African ancestry than among those of European ancestry but significantly more common among females of African ancestry than among those of European ancestry, cell lines demonstrate a similar dearth of African genomic ancestry.…”

“…41 This is concordant with recent results from Woods-Burnham and colleagues, who identified substantial African ancestry in a commercially available prostate cancer cell line with previously unknown ancestry, and noted the lack of racial diversity in commercially available prostate cancer cell lines. 7 In esophageal cancer, which is less common among males of African ancestry than among those of European ancestry but significantly more common among females of African ancestry than among those of European ancestry, 41 cell lines demonstrate a similar dearth of African genomic ancestry. Although endometrial cancer is more common and more severe among individuals of African ancestry, and has distinct molecular alterations in these individuals, [9][10][11][13][14][15] no endometrial cancer cell lines from our data set have any African ancestry.…”

“…Therefore, the National Institutes of Health (NIH) and other experts have placed an emphasis on improving cell line characterization, including genetically, so that phenotypic heterogeneity between cell types can be better controlled and research reproducibility and generalizability can be improved . One aspect of cancer cell line characterization that is notably lacking is the identification and annotation of ancestral composition . The Catalogue of Somatic Mutations in Cancer (COSMIC) (Wellcome Sanger Institute, Hinxton, UK) reports ancestry or race information for only approximately 30% of the >1000 cell lines they annotate and for which they provide genomic data.…”

“…[3][4][5][6] One aspect of cancer cell line characterization that is notably lacking is the identification and annotation of ancestral composition. 7 The Catalogue of Somatic Mutations in Cancer (COSMIC) 8 (Wellcome Sanger Institute, Hinxton, UK) reports ancestry or race information for only approximately 30% of the >1000 cell lines they annotate and for which Cancer June 15, 2019 they provide genomic data. With the remaining approximately 70% of COSMIC cell lines reporting unknown ancestral status, and with preclinical studies often failing to report the ancestral characterization of the cell lines they use, it is easy to imagine scenarios in which researchers use cell lines and/or cell line data that are not ancestrally representative of the patient populations for whom their findings are intended to apply.…”

Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans

“…RON is an RTK, also known as macrophage stimulating‐1 receptor (MST1R) shares structural similarities with c‐MET . Based on the recent report that castrate‐resistant PCa cell line 22Rv1 is of 41% of West African origin and 42% European in origin, we assessed expression and levels of RON and its homolog c‐MET using real‐time PCR and immunoblot analysis. We found that levels and expression of RON were higher in this cell line compared to LNCaP cells (derived from a Caucasian patient; Figure ).…”