The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index; 13 of the 34 sources its claims cite were checked for support.
Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines
Open accessAbstract
In recent years, biological research involving human cell lines has been rapidly developing in China. However, some of the cell lines are not authenticated before use. Therefore, misidentified and/or cross-contaminated cell lines are unfortunately commonplace. In this study, we present a comprehensive investigation of cross-contamination and misidentification for a panel of 278 cell lines from 28 institutes in China by using short tandem repeat profiling method. By comparing the DNA profiles with the cell bank databases of ATCC and DSMZ, a total of 46.0% (128/278) cases with cross-contamination/misidentification were uncovered coming from 22 institutes. Notably, 73.2% (52 out of 71) of the cell lines established by the Chinese researchers were misidentified and accounted for 40.6% of total misidentification (52/128). Further, 67.3% (35/52) of the misidentified cell lines established in laboratories of China were HeLa cells or a possible hybrid of HeLa with another kind of cell line. Furthermore, the bile duct cancer cell line HCCC-9810 and degenerative lung cancer Calu-6 exhibited 88.9% match in the ATCC database (9-loci), indicating that they were from the same origin. However, when we used 21-loci to compare these two cell lines with the same algorithm, the percent match was only 48.2%, indicating that these two cell lines were different. The SNP profiles of HCCC-9810 and Calu-6 also revealed that they were different cell lines. 150 cell lines with unique profiles demonstrated a wide range of in vitro phenotypes. This panel of 150 genomically validated cancer cell lines represents a valuable resource for the cancer research community and will advance our understanding of the disease by providing a standard reference for cell lines that can be used for biological as well as preclinical studies.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
STR profiling of 278 tumor cell lines from 28 institutes in China found that 46.0% (128/278) were cross-contaminated or misidentified, with Chinese-established lines especially affected (73.2%, 52/71). The study also shows that 21-loci STR plus SNP genotyping can distinguish HCCC-9810 and Calu-6, which 9-loci ATCC profiling falsely matched at 88.9%.
Key findings
- A total of 128/278 (46.0%) cross-contamination/misidentification cases were uncovered from 22 institutes; 20/278 (7.2%) failed PCR and were confirmed non-human, complete analysis succeeded for 258/278 (92.8%), and 150 cell lines were unique.
- Among cell lines established in China, 52/71 (73.2%) were misidentified, and 35/52 (67.3%) of those were HeLa or a possible HeLa hybrid; in the non-Chinese model, 64/193 (33.2%) were misidentified or cross-contaminated. Overall, HeLa caused 60/128 (46.9%) of cross-contamination, affecting 31 cell lines.
- HCCC-9810 and Calu-6 showed 88.9% match with the ATCC 9-loci database, but only 48.2% match with 21-loci STR; 24-loci SNP genotyping found 8 mismatches, indicating different origins.
- Genetic instability was observed: 69 HeLa cell lines showed one or more STR alterations versus the prototype; nine other lines (293, BxPC-3, HT-29, DLD-1, HCT-116, Jurkat, Raji, HeLa, 5637) shared 80–94.12% identity to original lines after multiple passages; 32 cell lines with microsatellite instability were identified.
Methods
- The authenticity of 278 tumor cell lines deposited in CCTCC by 28 institutes was examined; DNA was extracted and profiled using the Microreader TM21D System, co-amplifying 20 STR loci plus amelogenin, then compared with ATCC and DSMZ databases using the ATCC algorithm (≥80% related, <55% not related, 55–80% requiring further authentication).
- Sensitivity for intraspecies cross-contamination was tested with AsPC-1:HeLa mixtures at 99:1, 95:5, 90:10, and 80:20 ratios; species identification used 10 species-specific primer sets; HCCC-9810 and Calu-6 were further characterized by 24-loci SNP genotyping.
Limitations
- Stated: current STR databases such as ATCC, DSMZ, and JCRB provide only 9-loci profiles; 9 markers did not reliably discriminate HCCC-9810 and Calu-6, and authentication improved with 21-loci STR and SNP genotyping; the paper calls for careful and frequent authentication, possibly by more than one method.
- Evident: the sample consists of cell lines deposited in CCTCC from 28 institutes in China, so the rates may not generalize elsewhere; 20 non-human samples failed PCR and 14 cell lines lacked original background documents, limiting classification; some STR profiles were non-detectable; the text reports both 46.0% and 46.4% for the overall contamination rate.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Verification
Claims the paper makes
13 of 34 cited sources checked · 5 supported · 1 flagged · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Normal diploid cell lines, namely CCC-HIE-2, FHC and FSH-74int, established by the Chinese Academy of Medical Sciences [32, 33], respectively, had been shown to be actually derived from HeLa cells.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [32] KM Siddiqui, 1984, Primary and long term epithelial cell cultures from human fetal normal colonic mucosa, In vitro source
- Disputedcites [33] I Elisia, 2013, Modulation of NF-kappaB and Nrf2 control of inflammatory responses in FHs 74 Int cell line is tocopherol isoform-specific, American journal of physiology Gastrointestinal and liver physiology sourceExperimental — accuracy not yet measured
The Materials and Methods (Cell culture; page unavailable) describes FHs 74 Int as a primary cell line derived from a human fetal small intestine, contrary to the claim that it was derived from HeLa cells. Our copy does not address HeLa derivation of CCC-HIE-2 or FHC. (LLM, conf=0.84)
Checked by a reasoning model — may be wrong.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesEvery source the paper cites for this claim was checked and supports it.
In the paper
“Two adenoid cystic carcinoma, ACC-2 and ACC-M were reported as being contaminated by HeLa [22].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Most common contaminants
What the sources say
- Supportedcites [22] J Phuchareon, 2009, Genetic profiling reveals cross-contamination and misidentification of 6 adenoid cystic carcinoma cell lines: ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2, PloS one source
The Results section reports that ACC2 and ACCM matched HeLa cells by STR profiling and concludes that they were HeLa cells. The Discussion table also lists HeLa as the real identity of both cell lines. The paper additionally identifies ACC3, but that does not undermine the claim about ACC2 and ACCM. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The SNP genotyping at 24-loci showed that there were 8 mismatches loci between HCCC-9810 and Calu-6 cell line, suggesting that they were from different origins [30].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Identity of HCCC-9810 and Calu-6
What the sources say
- Partly supportedcites [30] F Castro, 2013, High-throughput SNP-based authentication of human cell lines, Int J Cancer sourceExperimental — accuracy not yet measured
The Results section ('Probability of discrimination and pair-wise analysis'; page unavailable) says that 0–2 mismatches across 24 SNPs indicate identical cell lines, supporting the inference that eight mismatches suggest different origins. Our copy does not report an eight-mismatch comparison between HCCC-9810 and Calu-6; searches for both cell-line names found no matching passage. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The SNP genotyping at 24-loci showed that there were 8 mismatches loci between HCCC-9810 and Calu-6 cell line, suggesting that they were from different origins [30].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Identity of HCCC-9810 and Calu-6
What the sources say
- Partly supportedcites [30] F Castro, 2013, High-throughput SNP-based authentication of human cell lines, Int J Cancer sourceExperimental — accuracy not yet measured
The Methods (MCA-SNP typing; Statistics, page unavailable) describe genotyping 24 SNP loci. The Results (Analysis of DSMZ cell line collection by MCA, page unavailable) confirm that all 24 loci could be typed simultaneously, but do not report a comparison of HCCC-9810 with Calu-6 or eight mismatches; searches for both cell-line names found no such result. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“WISH, which has been reported as a HeLa contaminant for decades [37], was also on the panel of cell models for differentiation [38] in these institutions under its false identity-amnion cell line of human origin.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Discussion
What the sources say
- Partly supportedcites [37] DA Kniss, 2014, Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research, Reproductive sciences sourceExperimental — accuracy not yet measured
The Introduction and Discussion (page numbers unavailable) identify WISH as an amnion-derived cell line contaminated with HeLa and report its use in reproductive-biology research. They do not say WISH was on a panel of models for differentiation at the institutions described in the citing sentence. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [38] XD Chen, 2012, Astragalus induces human amniotic epithelial cells (WISH) to differentiate toward neurons, inhibits the expression of Notch1 and promotes cell survival, Sheng li xue bao: [Acta physiologica Sinica]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“WISH, which has been reported as a HeLa contaminant for decades [37], was also on the panel of cell models for differentiation [38] in these institutions under its false identity-amnion cell line of human origin.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Discussion
What the sources say
- Partly supportedcites [37] DA Kniss, 2014, Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research, Reproductive sciences sourceExperimental — accuracy not yet measured
The Introduction and Discussion identify WISH as a cell line known to be contaminated with HeLa, and the paper reports confirming that contamination. The Discussion says HeLa contamination of cell lines has been reported for nearly 50 years, but it does not establish that WISH specifically had been reported as contaminated for decades; no page numbers are available in our copy. (LLM, conf=0.82)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“coming from 22 institutes”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Abstract
Strength:plain· not yet calibratedn = 128Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The 278 cell lines from 28 institutes in China are representative of widely used tumor cell lines in China.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a total of 46.0% (128/278) cases with cross-contamination/misidentification were uncovered coming from 22 institutes.”
- Also stated in: § Incidence and extent of cell line cross-contaminants · plain
“Altogether, 128 instances of cross-contamination were confirmed, with an incidence of 46.0% (128/278).”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The 278 cell lines from 28 institutes in China are representative of widely used tumor cell lines in China.
- Also stated in: § Incidence and extent of cell line cross-contaminants · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“73.2% (52 out of 71) of the cell lines established by the Chinese researchers were misidentified”
- Also stated in: § Incidence and extent of cell line cross-contaminants · boosted
“The remaining instances were unequivocally misidentified with an incidence of 73.2% (52 out of 71)”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The original descriptions or documents of cell lines accurately identify their tissue of origin and whether they were established in China.
- Also stated in: § Incidence and extent of cell line cross-contaminants · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the bile duct cancer cell line HCCC-9810 and degenerative lung cancer Calu-6 exhibited 88.9% match in the ATCC database (9-loci), indicating that they were from the same origin.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Abstract
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The ATCC and DSMZ cell bank STR databases used for comparison are accurate and authoritative references for cell line identity.
- Rests on an assumption: The match algorithm and similarity thresholds used to compare STR profiles correctly indicate whether two cell lines are the same or different.
- It may state two separate claims as one. 23
- Probably not a substantial claim. 7
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The bladder cancer cell line T24 was established in 1972 and has contributed to several cell line cross-contamination [20, 21].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Most common contaminants
What the sources say
- Partly supportedcites [20] G Johnen, 2013, Cross-contamination of a UROtsa stock with T24 cells—molecular comparison of different cell lines and stocks, PloS one sourceExperimental — accuracy not yet measured
The Discussion says T24 was established in 1973, not 1972. The Discussion and Introduction support the other part of the claim: they describe T24 as a frequent source of cell-line contamination and identify multiple affected lines. (LLM, conf=0.90)
- Could not verifycites [21] B Nabarra, 2005, Neoplastic transformation and angiogenesis in the thymus of transgenic mice expressing SV40 T and t antigen under an L-pyruvate kinase promoter (SV12 mice), International journal of experimental pathology sourceExperimental — accuracy not yet measured
The Abstract and Materials and methods describe SV12 transgenic mice and thymic tumours, not the T24 bladder cancer cell line. Searches for T24, its establishment in 1972, and cell-line cross-contamination found no passage addressing either part of the claim. (LLM, conf=0.75)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Microsatellite instability (MSI) was reported in leukemia [25], gastric [26], ovarian [27], breast [28], and colon cancers [29].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Genetic instability in vitro
What the sources say
- Not checked — no full text of the sourcecites [25] W Parson, 2005, Cancer cell line identification by short tandem repeat profiling: power and limitations, The FASEB journal source
- Supportedcites [26] Y Yao, 2004, Alterations of DNA mismatch repair proteins and microsatellite instability levels in gastric cancer cell lines, Laboratory investigation; a journal of technical methods and pathology source
Citation [26] is attached to “gastric,” not to the other cancer types. The paper’s Abstract reports MSI in gastric cancers, and its Discussion states that gastric carcinomas frequently display MSI. (LLM, conf=0.94)
- Supportedcites [27] S V, 2014, Microsatellite instability, promoter methylation and protein expression of the DNA mismatch repair genes in epithelial ovarian cancer, Genomics source
The citation to this paper is attached to “ovarian,” not to the other cancer types in the sentence. The Discussion reports MSI in ovarian cancers, and Results §2.1 documents MSI in the ovarian tumors studied. Page numbers are not provided in our copy. (LLM, conf=0.94)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“CNE-2, derived from the Chinese patients, was reported bearing HPV sequences and suspected to be contaminated by fusion of HeLa with another nasopharyngeal cell line [23].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Most common contaminants
What the sources say
- Supportedcites [23] SY Chan, 2008, Authentication of nasopharyngeal carcinoma tumor lines, International journal of cancer source
In “Dear Sir,” the paper reports that CNE-2 was originally established from a tumor of a Chinese patient and that HPV-18 sequences were detected in CNE-2. It postulates that the cell line arose through fusion of HeLa with an NPC cell line, consistent with the claim’s tentative wording. The Chinese-patient origin is the reported original provenance, not a confirmation that the tested cells remained authentic. (LLM, conf=0.92)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“including four examples that were notably false cell lines (U-251, Hep2, Ej and HBL-100) for which the actual identity had been previously reported [8–12], contributing 6.3% (4/64) of the contamination rate.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
What the sources say
- Not checked — no full text of the sourcecites [8] 2010, Cell line misidentification: the beginning of the end, Nature reviews Cancer source
- Not checked — no full text of the sourcecites [9] S Azari, 2007, Profiling and authentication of human cell lines using short tandem repeat (STR) loci: Report from the National Cell Bank of Iran, Biologicals: journal of the International Association of Biological Standardization source
- Partly supportedcites [10] PL Lorenzi, 2009, DNA fingerprinting of the NCI-60 cell line panel, Molecular cancer therapeutics sourceExperimental — accuracy not yet measured
The Introduction and Results and Discussion (Matching Profiles; page unavailable) report that SNB-19 is derived from U251, supporting a previously reported identity relationship involving U251. They do not identify U251 itself as a false cell line or address Hep2, Ej, HBL-100, the non-Chinese model, or the 6.3% (4/64) figure. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [11] JR Masters, 2001, Short tandem repeat profiling provides an international reference standard for human cell lines, Proceedings of the National Academy of Sciences of the United States of America source
- Not checked — no full text of the sourcecites [12] K Yoshino, 2006, Essential role for gene profiling analysis in the authentication of human cell lines, Human cell source
Strength:plain· not yet calibratedn = 60Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The HaCaT [34], HUVEC [35], SV-HUC-1[36], and hEM15A cell lines established from immortalized human skin cutis cells, umbilical cords, ureteral epithelium and endometrial stromal cells were totally free from cross-contamination.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Discussion
What the sources say
- Supportedcites [34] P Boukamp, 1988, Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line, The Journal of cell biology source
Citation [34] is attached to HaCaT, not to the other three cell lines. The Cytogenetic Characteristics passage (p. 764) says HaCaT’s markers excluded cross-contamination with other human cell lines developed or used in the authors’ laboratory; the Identity of HaCaT Cell and Donor DNA passage reports matching donor fingerprints and distinct fingerprints from other tested lines. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [35] SE Hughes, 1996, Functional characterization of the spontaneously transformed human umbilical vein endothelial cell line ECV304: use in an in vitro model of angiogenesis, Experimental cell research source
- Not checked — no full text of the sourcecites [36] CA Reznikoff, 1988, Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene, Carcinogenesis source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In sharp contrast, the subclones generated from K562 showed a high concordance of the clonotype homogeneity, i.e., one different clonotype was observed among the six K562 cell lines and the profile of the subclones differed from the parental culture by a single change of STR.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Genetic instability in vitro
Strength:plain· not yet calibratedn = 6Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Different samples of SGC-7901, SMMC-7721, BEL-7402, BEL-7404, BEL-7704, HL-7702, BGC-823 and TSCCA cell lines collected from independent laboratories were contaminated by either HeLa or another contaminant, possibly caused by a second intruder when they were cultured (Table 3).”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Most common contaminants
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“95 C was obtained from the primary tumor site while 95 D originated from lymph nodes of the metastatic site.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, when we used 21-loci to compare these two cell lines with the same algorithm, the percent match was only 48.2%, indicating that these two cell lines were different.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The match algorithm and similarity thresholds used to compare STR profiles correctly indicate whether two cell lines are the same or different.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two multilocus profiles revealed a close relationship between LNCaP and EJ, which was a vector for T24 cell line.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Most common contaminants
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The match algorithm and similarity thresholds used to compare STR profiles correctly indicate whether two cell lines are the same or different.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“129 instances out of 193 characterized samples had distinct STR profiles and consisted of 78 individual cell lines.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The ATCC and DSMZ cell bank STR databases used for comparison are accurate and authoritative references for cell line identity.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our findings showed evidence of 46.9% (60/128) cross-contamination was caused by HeLa, affecting 31 cell lines, which were purported to have been established from 10 types of tumor (colon, liver, breast, stomach, lung, nasopharynx, tougue, laryngeal, salivary gland and bronchia) and 3 types of normal tissue (lung, intestine and liver).”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Most common contaminants
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The subclones of these nine cell lines shared 80–94.12% identity to the original cell lines and appeared to bear null allele and mutations (Table 4).”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Genetic instability in vitro
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“84.4% (108/128) of cross-contamination was intra-species while 20 samples failed to be amplified by PCR and confirmed to be inter-species cross-contamination.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
Strength:plain· not yet calibratedn = 20Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 32 cell lines with MSI were identified with three banding patterns, including 7 liver cancer cell lines, 8 cervical cancer cell lines, 2 ovarian cancer cell lines, 1 leukemia cell line, 3 stomach cancer cell lines, 4 breast cancer cell lines, 1 colon cancer cell line, 2 osteosarcoma cancer cell lines, 1 pancreatic cancer cell line, 1 kidney cell line, 1 lung cancer cell line and 1 lymph”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Genetic instability in vitro
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the Chinese model, only 19 instances out of 71 had distinct STR profiles (26.8%) and consisted of 11 individual cell lines (Table 3).”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The original descriptions or documents of cell lines accurately identify their tissue of origin and whether they were established in China.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, vWA, D19S433, D16S539 and D13S317 loci were the least involved, showing three alleles at one locus.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Genetic instability in vitro
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CCTCC repository generated a new 21-loci STR database (www.CCTCC.org/STR.html)).”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Similarly, Zos and Zos-M were established respectively from the primary tumor site and the skip metastasis of an osteosarcoma patient [14].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
What the sources say
- Not checked — no full text of the sourcecites [14] C-y Zou, 2008, Establishment and characteristics of two syngeneic human osteosarcoma cell lines from primary tumor and skip metastases, Acta Pharmacologica Sinica source
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In contrast to the loss of heterozygosity, microsatellite instability [24], characterized by the occurrence of new alleles in tumors, is a major event in certain carcinomas brought about by mismatch repair deficiency.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Genetic instability in vitro
What the sources say
- Not checked — no full text of the sourcecites [24] H Yamamoto, 2015, Microsatellite instability: an update, Archives of toxicology source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This discrepancy could be resulted from either a technical issue in PCR, in which one allele was preferentially amplified while another was below the detectable level, or a biological variation where the Jurkat cell line from one laboratory had lost one allele.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Genetic instability in vitro
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“HCCLM-3 was a tumorigenic subclone of MHCC-97L and MHCC-97H, and was established from nude mice [15].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
What the sources say
- Not checked — no full text of the sourcecites [15] J Yang, 2005, Molecular cytogenetic characteristics of the human hepatocellular carcinoma cell line HCCLM3 with high metastatic potential: comparative genomic hybridization and multiplex fluorescence in situ hybridization, Cancer genetics and cytogenetics source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Since Y chromosome was unstable, some cell lines and even normal cells from older male donors lost the Y chromosome [13], such as A549 and Jurkat cell line.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Incidence and extent of cell line cross-contaminants
What the sources say
- Not checked — no full text of the sourcecites [13] HG Drexler, 2002, Bladder carcinoma cell line ECV304 is not a model system for endothelial cells, In Vitro Cellular & Developmental Biology-Animal source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“HeLa [16] and its derivatives HeLa S3, AV3 [17] and WISH contaminations are notorious problems and may be simply detected by either isoenzyme [18] or STR profiling [19].”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Results > Most common contaminants
What the sources say
- Not checked — no full text of the sourcecites [16] J Fogh, 1977, Absence of HeLa cell contamination in 169 cell lines derived from human tumors, Journal of the National Cancer Institute source
- Not checked — no full text of the sourcecites [17] JR Masters, 2002, HeLa cells 50 years on: the good, the bad and the ugly, Nature reviews Cancer source
- Not checked — no full text of the sourcecites [18] SM Gartler, 1968, Apparent Hela cell contamination of human heteroploid cell lines, Nature source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“An alarming rate of cross-contamination among human cell lines used in China was reported by Fang Ye and colleagues [6] who investigated 380 human cell lines in which about 25% was cross-contaminated or misidentified.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [6] F Ye, 2015, Genetic profiling reveals an alarming rate of cross-contamination among human cell lines used in China, FASEB journal: official publication of the Federation of American Societies for Experimental Biology source
Strength:plain· not yet calibratedn = 380Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each sample was repeated at least twice to confirm the results.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Materials and Methods > DNA extraction and STR profiling
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For data comparison, well-characterized and validated reference data obtained from ATCC and DSMZ were used.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Materials and Methods > DNA extraction and STR profiling
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“If the sample could not be amplified in three time repeats, it will be considered as non-human origin.”
§ Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines > Materials and Methods > DNA extraction and STR profiling
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
The paper relies on this without support.
The ATCC and DSMZ cell bank STR databases used for comparison are accurate and authoritative references for cell line identity.
“By comparing the DNA profiles with the cell bank databases of ATCC and DSMZ”
“had authenticated prototypes deposited in cell repositories or research institutions worldwide”
The paper relies on this without support.
The original descriptions or documents of cell lines accurately identify their tissue of origin and whether they were established in China.
“The verified cell lines were derived from 20 different tissues (Table 2).”
The paper relies on this without support.
The 278 cell lines from 28 institutes in China are representative of widely used tumor cell lines in China.
“a panel of 278 cell lines from 28 institutes in China”
“278 samples collected from 28 independent sources of China are divided into 2 groups”
The paper relies on this without support.
A unique STR profile is sufficient to consider a cell line genomically validated and suitable as a reference.
“150 cell lines with unique profiles demonstrated a wide range of in vitro phenotypes.”
“This panel of 150 genomically validated cancer cell lines represents a valuable resource”
The paper relies on this without support.
The match algorithm and similarity thresholds used to compare STR profiles correctly indicate whether two cell lines are the same or different.
“when we used 21-loci to compare these two cell lines with the same algorithm, the percent match was only 48.2%, indicating that these two cell lines were different.”
“The pairwise comparison of STR profiles revealed three matched pairs with similarity scores >0.9.”
The paper relies on this without support.
The misidentification and cross-contamination of cell lines are a widespread problem in research, dating back as far as 45 years ago.
“The misidentification and cross-contamination of cell lines are deemed to be a widespread problem in research, dating back as far as 45 years ago.”
The paper relies on this without support.
Spontaneous immortalization is rare in human cell lines.
“Instructively, spontaneous immortalization is rare in human cell lines.”
The paper relies on this without support.
Current STR databases such as ATCC, DSMZ and JCRB only provide 9-loci STR profiles.
“Unfortunately, currant STR databases such as ATCC, DSMZ and JCRB only provide 9-loci STR profiles.”
The paper relies on this without support.
Tainted cell lines are still on sale for use.
“Despite sporadic reports about cell line cross-contamination provided by cell repositories in China through systematic quality control check of their own cell lines, the tainted cell lines are still on sale for use.”
The paper relies on this without support.
The grave problem of cell line misidentification in China has been neglected.
“The grave problem of cell line misidentification in China has been neglected.”
The paper relies on this without support.
Lack of information has prevented researchers from keeping up to date with literature reports of cell line misidentification.
“Lack of information has prevented researchers from keeping up to date with literature reports of cell line misidentification.”
The paper relies on this without support.
The grave problem continues to fester due to the negligence of cell line users and originators as well as journal editors and funding agencies.
“Although the international cell repositories have compiled a list of cross-contaminated cell lines to alert their users, the grave problem continues to fester due to the negligence of cell line users and originators as well as journal editors and funding agencies.”
The paper relies on this without support.
STR-based profiling methods have been used for the authentication of cell lines for more than 24 years.
“STR-based profiling methods have been used for the authentication of cell lines for more than 24 years.”
The paper relies on this without support.
There are variations in the numbers of loci and in the specific loci comprising the published profiling.
“However, there are variations in the numbers of loci and in the specific loci comprising the published profiling.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Some studies have shown that misidentification and mycoplasma contamination are still common issues (Horbach and Halffman, 2017; Huang et al., 2017; Olarerin-George and Hogenesch, 2015; Timenetsky et al., 2006).”
From Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility (2024) · cites this paper as Huang et al., 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“several recent publications indicate levels of cell line contamination for China between 25% [13] and 46% [46]”
From The ghosts of HeLa: How cell line misidentification contaminates the scientific literature (2017) · cites this paper as [46]
The cited source says what the claim attributes to it.
In the citing paper
“Again, the CCCM rate among Chinese-derived cell lines was much higher: 73.2% (52/71) [104].”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [104]
The cited source says what the claim attributes to it.
In the citing paper
“Two years later, a 21-STR evaluation of 278 lines originating from 28 Chinese sources found a CCCM rate of 46% (128/278); 22 of the sources had contributed contaminated lines [104].”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [104]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“A member of the World Federation for Culture Collections (”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [104]
Experimental — accuracy not yet measured
In the citing paper
“Two NV identifiers (BGC-803, BSG-823) were recognized misspellings (26) of the contaminated cell lines BGC-823 or MGC-803 (38–41)”
From Misspellings or “miscellings”—Non‐verifiable and unknown cell lines in cancer research publications (2024) · cites this paper as [39]
In the citing paper
“This revealed that in 185/420 (44%) papers, all 8 NV identifiers could represent misspellings of similarly named cell lines, which were typically HeLa-contaminated cancer cell lines (38–41).”
From Misspellings or “miscellings”—Non‐verifiable and unknown cell lines in cancer research publications (2024) · cites this paper as [39]
In the citing paper
“and 3 NV cell lines (BGC-803, GSE-1, MGC-823) were described as sourced from the China Center for Type Culture Collection (38–41).”
From Misspellings or “miscellings”—Non‐verifiable and unknown cell lines in cancer research publications (2024) · cites this paper as [39]
In the citing paper
“These NV cell lines were also not described by studies describing STR profiles for similarly named contaminated cell lines (38–41).”
From Misspellings or “miscellings”—Non‐verifiable and unknown cell lines in cancer research publications (2024) · cites this paper as [39]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
STR locus name differs between methods and results
MinorThe methods identify D16S1043 as one of the amplified loci, whereas the results tables label that locus D6S1043.
“namely Penta D, Penta E, D19S433, D16S1043, D2S441, D12S391, D2S1338”
“| D18S51 | D6S1043 | AMEL |”
SNP assayed in Table 6 differs from the selected-SNP list
MinorThe methods list rs1800896 among the 24 selected SNPs, but the 24-locus results table reports rs1800869 instead. The text does not establish whether these are meant to be the same assay.
“rs1800896, rs1800872, rs1805010”
“| rs1800869 | G | G |”
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Metadata
- Authors
- Huang, Y., Liu, Y., Zheng, C., & Shen, C.
- Affiliations
- Wuhan University (CN)
- Corresponding author
- Zheng, Congyi
- Shen, Chao
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-01-20
- Volume
- 12
- Issue
- 1
- Pages
- e0170384
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5249119
- OpenAlex
- W2574356023
- Semantic Scholar
- 31b0e5a474894e03ce42b50eedbb3b34366a26db
- Cited by
- 105
- References
- 40
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 25 · 2023: 8 · 2022: 11 · 2021: 12 · 2020: 9 · 2019: 7 · 2018: 11 · 2017: 5
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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
- National Natural Sciences Foundation of China (31370185)
- National Basic Research Program of China (NSTI-CR14, NSTI-CR15)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Identification and Quantification in Food
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- cancer cell lines, cross-contamination, cell line misidentification, short tandem repeat profiling, cell line authentication, HeLa cells
- MeSH terms
- China, Humans, Neoplasms, Genomic Instability, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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