Genetic Profiling Reveals Cross-Contamination and Misidentification of 6 Adenoid Cystic Carcinoma Cell Lines: ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2
Open accessAbstract
Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm of the salivary glands. Most patients survive more than 5 years after surgery and postoperative radiation therapy. The 10 year survival rate, however, drops to 40%, due to locoregional recurrences and distant metastases. Improving long-term survival in ACC requires the development of more effective systemic therapies based on a better understanding of the biologic behavior of ACC. Much preclinical research in this field involves the use of cultured cells and, to date, several ACC cell lines have been established. Authentication of these cell lines, however, has not been reported. We performed DNA fingerprint analysis on six ACC cell lines using short tandem repeat (STR) examinations and found that all six cell lines had been contaminated with other cells. ACC2, ACC3, and ACCM were determined to be cervical cancer cells (HeLa cells), whereas the ACCS cell line was composed of T24 urinary bladder cancer cells. ACCNS and CAC2 cells were contaminated with cells derived from non-human mammalian species: the cells labeled ACCNS were mouse cells and the CAC2 cells were rat cells. These observations suggest that future studies using ACC cell lines should include cell line authentication to avoid the use of contaminated or non-human cells.
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Two adenoid cystic carcinoma, ACC-2 and ACC-M were reported as being contaminated by HeLa.
“Two adenoid cystic carcinoma, ACC-2 and ACC-M were reported as being contaminated by HeLa [22].”
From Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines (2017) · cites this paper as [22]
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“A previous study suggested that ACCs may exhibit similarities with HeLa cells (30).”
BackgroundKeysar, S. B., Eagles, J. R., Miller, B., Jackson, B. C., Chowdhury, F. N., Reisinger, J., Chimed, T.-S., Le, P. N., Morton, J. J., Somerset, H., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3871 · Cited by 33 · see citing works
“These already limited models are further diluted by disease histotype (4) and cell line misidentification (5).”
BackgroundDevelopment and characterization of salivary adenoid cystic carcinoma cell line
Li, J., Perlaky, L., Rao, P. H., Weber, R. S., & El‐Naggar, A. K. (2014) · Oral Oncology · doi:10.1016/j.oraloncology.2014.06.012 · Cited by 32 · see citing works
“STR DNA fingerprinting assay was conducted by the CCSG Characterized Cell Line Core at MD Anderson Cancer Center as previously described [15,20].”
MethodRadiosensitization of Adenoid Cystic Carcinoma with MDM2 Inhibition
Prabakaran, P. J., Javaid, A. M., Swick, A. D., Werner, L. R., Nickel, K. P., Sampene, E., Hu, R., Ong, I. M., Bruce, J. Y., Hartig, G. K., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0969 · Cited by 32 · see citing works
Head and neck adenoid cystic carcinoma
Bell, D., & Hanna, E. Y. (2012) · Current Opinion in Otolaryngology & Head & Neck Surgery · doi:10.1097/moo.0b013e32835c05fd · Cited by 30 · see citing works
MYB-activated models for testing therapeutic agents in adenoid cystic carcinoma
Jiang, Y., Gao, R., Cao, C., Forbes, L., Li, J., Freeberg, S., Fredenburg, K. M., Justice, J. M., Silver, N. L., Wu, L., et al. (2019) · Oral Oncology · doi:10.1016/j.oraloncology.2019.09.005 · Cited by 29 · see citing works
“Despite the direct evidence for structural MYB rearrangements, it has been difficult to generate validated human ACC tumor cell lines (31) and there are no activated MYB mouse models that recapitulate ACC salivary gland tumors.”
BackgroundSalivary glands adenoid cystic carcinoma: a molecular profile update and potential implications
da Silva, F. J., de Azevedo, J. C., Ralph, A. C. L., Pinheiro, J. D. J. V., Freitas, V. M., & Calcagno, D. Q. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1191218 · Cited by 28 · see citing works
“In vitro, assays are also insufficient due to the few established cell lines, and some have proven cross-contamination (82).”
BackgroundPanaccione, A., Zhang, Y., Ryan, M. R., Moskaluk, C. A., Anderson, K. S., Yarbrough, W. G., & Ivanov, S. V. (2017) · Stem Cell Research · doi:10.1016/j.scr.2017.05.002 · Cited by 25 · see citing works
“Unfortunately, most ACC cell lines generated 20–30 years ago and shared between laboratories turned out to be grossly contaminated or misidentified (Phuchareon et al., 2009; PLoS One, 2014).”
Korch, C. T., & Capes-Davis, A. (2021) · SLAS Discovery · doi:10.1177/24725552211051963 · Cited by 23 · see citing works
Phuchareon, J., Overdevest, J. B., McCormick, F. P., Eisele, D. W., van Zante, A., & Tetsu, O. (2014) · Translational Oncology · doi:10.1016/j.tranon.2014.10.003 · Cited by 23 · see citing works
Self-citationAuthentication of human cell-based products: the role of a new consensus standard
Kerrigan, L., & Nims, R. W. (2011) · Regenerative Medicine · doi:10.2217/rme.11.5 · Cited by 23 · see citing works
Zheng, C., Qiao, B., Wang, M., & Tao, Q. (2012) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/j.kjms.2012.09.001 · Cited by 21 · see citing works
“Currently, the most effective treatment for ACC is a combination therapy involving surgery, postoperative radiation, and chemotherapy [4].”
BackgroundTargeting MDM2 for Treatment of Adenoid Cystic Carcinoma
Warner, K. A., Nör, F., Acasigua, G. A., Martins, M. D., Zhang, Z., McLean, S. A., Spector, M. E., Chepeha, D. B., Helman, J. I., Wick, M. J., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1698 · Cited by 21 · see citing works
“The Tetsu laboratory reported contamination and misidentification of six established ACC cell lines (16).”
BackgroundPhuchareon, J., van Zante, A., Overdevest, J. B., McCormick, F. P., Eisele, D. W., & Tetsu, O. (2014) · Translational Oncology · doi:10.1016/j.tranon.2014.07.006 · Cited by 20 · see citing works
Self-citationOptimization of cell lines as tumour models by integrating multi-omics data
Zhao, N., Liu, Y., Wei, Y., Yan, Z., Zhang, Q., Wu, C., Chang, Z., & Xu, Y. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw082 · Cited by 20 · see citing works
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“Generally, primary cells retain cellular functions, growth characteristics, cellular markers and signaling pathways more similar to the original tissue when propagated in culture (Berwald and Sachs 1963; Phuchareon et al. 2009; Romano et al. 2009, ZenBio Scientific Publications 2015).”
BackgroundHarvesting Human Prostate Tissue Material and Culturing Primary Prostate Epithelial Cells
Frame, F. M., Pellacani, D., Collins, A. T., & Maitland, N. J. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3724-0_12 · Cited by 18 · see citing works
Andreasen, S., Agander, T. K., Bjørndal, K., Erentaite, D., Heegaard, S., Larsen, S. R., Melchior, L. C., Tan, Q., Ulhøi, B. P., Wessel, I., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24800 · Cited by 18 · see citing works
“As previous in vitro studies on the involvement of miRNA in the metastatic progression of ACC has been hampered by cross-contamination, data from human samples has not been available until now [15].”
BackgroundEstablishment, authenticity, and characterization of cervical cancer cell lines
Martinez, M. D. L. Z., Mendoza, C. M. L., Salazar, J. T., García-Carrancá, A. M., Cervantes, M. A. C., & Alcántara-Quintana, L. E. (2022) · Molecular & Cellular Oncology · doi:10.1080/23723556.2022.2078628 · Cited by 17 · see citing works
Johnen, G., Rozynek, P., von der Gathen, Y., Bryk, O., Zdrenka, R., Johannes, C., Weber, D. G., Igwilo-Okuefuna, O., Raiko, I., Hippler, J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064139 · Cited by 17 · see citing works
Korch, C. T., & Varella‐Garcia, M. (2018) · Advances in Molecular Pathology · doi:10.1016/j.yamp.2018.07.003 · Cited by 16 · see citing works
Authentication of the R06E Fruit Bat Cell Line
Jordan, I., Munster, V. J., & Sandig, V. (2012) · Viruses · doi:10.3390/v4050889 · Cited by 16 · see citing works
Yarbrough, W. G., Panaccione, A., Chang, M. T., & Ivanov, S. V. (2016) · Laryngoscope Investigative Otolaryngology · doi:10.1002/lio2.22 · Cited by 16 · see citing works
Stawarz, K., Durzyńska, M., Galazka, A., Gorzelnik, A., Zwoliński, J., Paszkowska, M., Bieńkowska‐Pluta, K., & Misiak-Gałązka, M. (2025) · Oncology Letters · doi:10.3892/ol.2025.14899 · Cited by 15 · see citing works
“The ACC2, ACC3 and ACCM cell lines were primarily contaminated with cervical cancer cells, while the ACCS cell line was composed of T24 urinary bladder cancer cells (11).”
Wang, S. J., Asthana, S., van Zante, A., Heaton, C. M., Phuchareon, J., Stein, L. C., Higuchi, S., Kishimoto, T., Chiu, C. Y., Olshen, A. B., et al. (2017) · Oral Oncology · doi:10.1016/j.oraloncology.2017.03.020 · Cited by 14 · see citing works
“Cell culture The following cell lines were from the American Type Culture Collection: SCC-4, SCC-25, CAL27, HeLa, SW480, 293T, and WI-38.”
BackgroundInfluentialSelf-citationMolecular features of adenoid cystic carcinoma with an emphasis on micro RNA expression
Andreasen, S. (2018) · Apmis · doi:10.1111/apm.12828 · Cited by 14 · see citing works
“in vitro studies, but the cell lines used have since been shown to be severely contaminated with various non-ACC cells (153).”
BackgroundCai, C., Rodepeter, F. R., Rossmann, A., Teymoortash, A., Lee, J.-S., Quint, K., Fazio, P. D., Ocker, M., Werner, J. A., & Mandić, R. (2012) · PubMed · Cited by 14 · see citing works
Schweppe, R. E. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00081 · Cited by 13 · see citing works
Persson, M., Andersson, M. K., Sahlin, P., Mitani, Y., Brandwein‐Weber, M., Frierson, H. F., Moskaluk, C. A., Fonseca, I., Ferrarotto, R., Boecker, W., et al. (2023) · The Journal of Pathology · doi:10.1002/path.6172 · Cited by 13 · see citing works
Guarracino, M. R., Xanthopoulos, P., Pyrgiotakis, G., Tomaino, V., Moudgil, B. M., & Pardalos, P. M. (2011) · Artificial Intelligence in Medicine · doi:10.1016/j.artmed.2011.07.002 · Cited by 13 · see citing works
“To his day, the most accurate way of discriminating among various ells is through genetic profiling (gene expression) [7] or identificaion with biomarkers, which can take long time, requires expensive quipment and trained personnel [8].”
BackgroundIGRhCellID: integrated genomic resources of human cell lines for identification
Shiau, C.-K., Gu, D.-L., Chen, C., Lin, C.-H., & Jou, Y. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1075 · Cited by 12 · see citing works
Girolamo, N. D., Chow, S., Richardson, A., & Wakefield, D. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18783 · Cited by 12 · see citing works
Robustin-silicoidentification of cancer cell lines based on next generation sequencing
Otto, R., Sers, C., & Leser, U. (2017) · Oncotarget · doi:10.18632/oncotarget.16110 · Cited by 12 · see citing works
“Oncotarget34315www.impactjournals.com/oncotarget Three factors have been found to be associated with false negative (FN) predictions: About 100 of the 546 FN-predictions for weight 1.0 occurred between queryreference pairs that were defined as identical by the goldstandard due to either cross-contamination (e.g. ACCS…”
BackgroundInfluentialRoth, J. S., Lee, T. D., Cheff, D. M., Gosztyla, M. L., Asawa, R. R., Danchik, C., Michael, S., Simeonov, A. M., Klumpp-Thomas, C. A., Wilson, K. M., et al. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220911451 · Cited by 15 · see citing works
Establishment and genomic characterization of primary salivary duct carcinoma cell line
Li, J., Mitani, Y., Rao, P. H., Perlaky, L., Liu, B., Weber, R. S., & El‐Naggar, A. K. (2017) · Oral Oncology · doi:10.1016/j.oraloncology.2017.04.007 · Cited by 11 · see citing works
Adenoid cystic carcinoma: insights from molecular characterization and therapeutic advances
Jia, Y., Liu, Y., Yang, H., & Yao, F. (2024) · MedComm · doi:10.1002/mco2.734 · Cited by 10 · see citing works
The Epigenesis of Salivary Glands Carcinoma: From Field Cancerization to Carcinogenesis
Lazim, N. M., Yousaf, A., Abusalah, M. A. H., Sulong, S., Ismail, Z. I. M., Mohamud, R., Abu-Harirah, H. A., AlRamadneh, T. N., Hassan, R., & Abdullah, B. (2023) · Cancers · doi:10.3390/cancers15072111 · Cited by 9 · see citing works
Ling, S., Rettig, E. M., Tan, M., Chang, X., Wang, Z., Brait, M., Bishop, J. A., Fertig, E. J., Considine, M., Wick, M. J., et al. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3532 · Cited by 9 · see citing works
“Our approach was to circumvent the lack of viable ACC cell lines (20) by using primary xenograft tumor models, in an attempt to identify relevant genes exhibiting differential promoter methylation.”
MethodThe cross-contaminated cell lines of adenoid cystic carcinoma: A crucial concern
Chen, W., Liu, N., & Zhang, S.-L. (2017) · Translational Surgery · doi:10.4103/2468-5585.200513 · Cited by 8 · see citing works
Dožić, B., Glumac, S., Boričić, N., Dožić, M., Aničić, B., & Boričić, I. (2016) · PubMed · Cited by 8 · see citing works
Elevated TARP promotes proliferation and metastasis of salivary adenoid cystic carcinoma
Yue, H., Cai, Y., Song, Y., Meng, L., Chen, X., Wang, M., Bian, Z., & Wang, R. (2016) · Oral Surgery Oral Medicine Oral Pathology and Oral Radiology · doi:10.1016/j.oooo.2016.11.023 · Cited by 7 · see citing works
Establishment and characterization of an orthotopic sinonasal squamous cell carcinoma mouse model
Costales, M., López, F., García–Inclán, C., Fernández, S., Marcos, C. Á., Llorente, J. L., & Hermsen, M. A. J. A. (2014) · Head & Neck · doi:10.1002/hed.23832 · Cited by 6 · see citing works
“Gelbard et al(21) used 2 aggressive tumor cell lines: DM14 is a highly metastatic clone of cell line TU167 of an SCC of the floor of the mouth, and ACC3 was, in fact, not an adenoid cystic carcinoma cell line, but HeLa.(23,24) Our cell line, SCCNC4, was derived from a T2N1M0 primary maxillary sinus SCC.”
MethodXia, R., Wang, Z., Zhang, C., Hu, Y., Zhou, R., Wang, L., Tian, Z., & Jiang, L. (2015) · Oral Surgery Oral Medicine Oral Pathology and Oral Radiology · doi:10.1016/j.oooo.2015.04.015 · Cited by 6 · see citing works
Challenges and Advances in the Development of Cell Lines and Xenografts
Schweppe, R. E., & Korch, C. T. (2018) · Advances in Molecular Pathology · doi:10.1016/j.yamp.2018.07.004 · Cited by 6 · see citing works
Human Cell Line Authentication: The Critical First Step in Any Project Using Human Cell Lines
McLaren, R. S., Reid, Y. A., & Storts, D. R. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-230-8_21 · Cited by 5 · see citing works
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Rose, A. J., Fleming, M. M., Francis, J. C., Ning, J., Patrikeev, A., Chauhan, R., Harrington, K. J., & Swain, A. (2023) · The Journal of Pathology · doi:10.1002/path.6209 · Cited by 4 · see citing works
“There are few bona fi de ACC cell lines, and most do not retain consistent MYB expression if a translocation is present [17,18].”
BackgroundSodium Iodide Symporter Expression in Adenoid Cystic Carcinoma of the Head and Neck
Gainor, D. L., Chute, D. J., & Lorenz, R. R. (2015) · JAMA Otolaryngology–Head & Neck Surgery · doi:10.1001/jamaoto.2015.0970 · Cited by 4 · see citing works
Warner, K. A., Sahara, S., Herzog, A. E., Nör, F., CASTILHO, R. M., Polverini, P. J., & Nor, J. E. (2025) · Frontiers in Oral Health · doi:10.3389/froh.2025.1570042 · Cited by 3 · see citing works
“Phuchareon and colleagues identi fi ed the cross contamination of 6 ACC cell lines widely used to study this disease (47).”
Slivar, I. D. S., Zanesco, B. D. A., Martins, M. D., Matos, L. L., Nunes, F. D., Schuch, L. F., & Wagner, V. P. (2025) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.70028 · Cited by 3 · see citing works
“While the organoids have been obtained from ACC validated patient-derived xenograft (PDX) models, caution must be taken in the analysis of the second study as the cell line used (ACCM) has been shown to be contaminated with HeLa [32].”
Transcriptomic Prediction of Pig Liver-Enriched Gene 1 Functions in a Liver Cell Line
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- Authors
- Phuchareon, J., Ohta, Y., Woo, J. M., Eisele, D. W., & Tetsu, O.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Tetsu, Osamu
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-06-25
- Volume
- 4
- Issue
- 6
- Pages
- e6040
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2698276
- OpenAlex
- W2000248995
- Cited by
- 105
- References
- 46
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 10 · 2017: 14 · 2016: 10 · 2015: 5 · 2014: 7 · 2013: 10 · 2012: 9
- FWCI
- 7.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Adenoid Cystic Carcinoma Research Foundation
- Johns Hopkins University
- University of California, San Francisco
- Topics
- Health Sciences › Medicine › Surgery › Salivary Gland Tumors Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Identification and Quantification in Food
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- adenoid cystic carcinoma, cell line contamination, cell line authentication, short tandem repeat profiling, DNA fingerprinting, HeLa cells, T24 cells, salivary gland carcinoma
- MeSH terms
- Alleles, Animals, Urinary Bladder Neoplasms, Carcinoma, Adenoid Cystic, Electron Transport Complex IV, HeLa Cells, Humans, Salivary Gland Neoplasms, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, Cell Line, Tumor, Mice, Rats
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