TY - JOUR
T1 - DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination
AU - Korch, Christopher
AU - Spillman, Monique A.
AU - Jackson, Twila A.
AU - Jacobsen, Britta M.
AU - Murphy, Susan K.
AU - Lessey, Bruce A.
AU - Jordan, V. Craig
AU - Bradford, Andrew P.
N1 - Funding Information:
We are grateful to the investigators who generously provided cell lines for analysis. STR profiling and sequence analysis were carried out in the University of Colorado Cancer Center (UCCC) DNA Sequencing and Analyses Core. We thank Dr. Marileila Varella Garcia of the UCCC Molecular Pathology Shared Resource Cytogenetics Core (NCI-P30CA046934) for karyotype comparison and analysis and Jerry Haney for MSI assays. This work was funded in part by NCI CA125427 , NICHD HD06772 1, Lombardi Comprehensive Cancer Center support grant NIH P30 CA051008 , Department of Defense grant W81XWH-11-1-0469 , Cancer League of Colorado , Ovarian Cancer Research Fund , Foundation for Women's Cancer , Adelson Family Cancer Foundation and University of Colorado Department of Obstetrics and Gynecology .
PY - 2012/10
Y1 - 2012/10
N2 - Objectives: Cell lines derived from human ovarian and endometrial cancers, and their immortalized non-malignant counterparts, are critical tools to investigate and characterize molecular mechanisms underlying gynecologic tumorigenesis, and facilitate development of novel therapeutics. To determine the extent of misidentification, contamination and redundancy, with evident consequences for the validity of research based upon these models, we undertook a systematic analysis and cataloging of endometrial and ovarian cell lines. Methods: Profiling of cell lines by analysis of DNA microsatellite short tandem repeats (STR), p53 nucleotide polymorphisms and microsatellite instability was performed. Results: Fifty-one ovarian cancer lines were profiled with ten found to be redundant and five (A2008, OV2008, C13, SK-OV-4 and SK-OV-6) identified as cervical cancer cells. Ten endometrial cell lines were analyzed, with RL-92, HEC-1A, HEC-1B, HEC-50, KLE, and AN3CA all exhibiting unique, uncontaminated STR profiles. Multiple variants of Ishikawa and ECC-1 endometrial cancer cell lines were genotyped and analyzed by sequencing of mutations in the p53 gene. The profile of ECC-1 cells did not match the EnCa-101 tumor, from which it was reportedly derived, and all ECC-1 isolates were genotyped as Ishikawa cells, MCF-7 breast cancer cells, or a combination thereof. Two normal, immortalized endometrial epithelial cell lines, HES cells and the hTERT-EEC line, were identified as HeLa cervical carcinoma and MCF-7 breast cancer cells, respectively. Conclusions: Results demonstrate significant misidentification, duplication, and loss of integrity of endometrial and ovarian cancer cell lines. Authentication by STR DNA profiling is a simple and economical method to verify and validate studies undertaken with these models.
AB - Objectives: Cell lines derived from human ovarian and endometrial cancers, and their immortalized non-malignant counterparts, are critical tools to investigate and characterize molecular mechanisms underlying gynecologic tumorigenesis, and facilitate development of novel therapeutics. To determine the extent of misidentification, contamination and redundancy, with evident consequences for the validity of research based upon these models, we undertook a systematic analysis and cataloging of endometrial and ovarian cell lines. Methods: Profiling of cell lines by analysis of DNA microsatellite short tandem repeats (STR), p53 nucleotide polymorphisms and microsatellite instability was performed. Results: Fifty-one ovarian cancer lines were profiled with ten found to be redundant and five (A2008, OV2008, C13, SK-OV-4 and SK-OV-6) identified as cervical cancer cells. Ten endometrial cell lines were analyzed, with RL-92, HEC-1A, HEC-1B, HEC-50, KLE, and AN3CA all exhibiting unique, uncontaminated STR profiles. Multiple variants of Ishikawa and ECC-1 endometrial cancer cell lines were genotyped and analyzed by sequencing of mutations in the p53 gene. The profile of ECC-1 cells did not match the EnCa-101 tumor, from which it was reportedly derived, and all ECC-1 isolates were genotyped as Ishikawa cells, MCF-7 breast cancer cells, or a combination thereof. Two normal, immortalized endometrial epithelial cell lines, HES cells and the hTERT-EEC line, were identified as HeLa cervical carcinoma and MCF-7 breast cancer cells, respectively. Conclusions: Results demonstrate significant misidentification, duplication, and loss of integrity of endometrial and ovarian cancer cell lines. Authentication by STR DNA profiling is a simple and economical method to verify and validate studies undertaken with these models.
KW - Authenticity
KW - Cell lines
KW - Endometrial
KW - Ovarian
KW - STR profiling
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U2 - 10.1016/j.ygyno.2012.06.017
DO - 10.1016/j.ygyno.2012.06.017
M3 - Article
C2 - 22710073
AN - SCOPUS:84865694064
SN - 0090-8258
VL - 127
SP - 241
EP - 248
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 1
ER -