Abstract
A variety of analytical approaches have indicated that melanoma cell line UCLA‐SO‐M14 (M14) and breast carcinoma cell line MDA‐MB‐435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross‐contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA‐MB‐435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA‐MB‐435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA‐MB‐435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA‐MB‐435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research.
Highlights
What’s new? A variety of analytical approaches have indicated that melanoma cell line M14 and breast carcinoma cell line MDA-MB-435 originate from a common donor, but there is ongoing debate regarding which is the misidentified cell line
Cell line provenance shows that M14 was established before MDA-MB-435 The International Cell Line Authentication Committee (ICLAC) maintains a list of known misidentified cell lines based on testing and known provenance
M14 was reported to be established at the University of California Los Angeles (UCLA) from a 33-year-old patient with metastatic melanoma; tissue was removed from an amelanotic lesion on the right buttock
Summary
Numerous analytical approaches (karyotyping, comparative genomic hybridization, microsatellite polymorphism analysis, STR analysis, single nucleotide polymorphism (SNP) analysis and bioinformatics analysis of gene expression) have demonstrated that the MDA-MB-435 cell line shares a common origin with the M14 melanoma cell line.[4,5] These studies have concluded that MDA-MB-435 is misidentified and is a derivative of the M14 melanoma cell line.[4,6,7,8]. This conclusion, has been debated on the basis of phenotypic evidence. MDA-MB-435 can express breastspecific and epithelial-specific markers, leading to the conclusion that it is derived from breast carcinoma and that expression of melanocyte-specific markers may be caused by lineage infidelity,[9,10] possibly as a normal property of freshly excised mammary tumor tissue.[11]
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