Beware Imposters: Ma-1, A Novel Malt Lymphoma Cell Line, Is Misidentified And Corresponds To Pfeiffer, A Diffuse Large B-Cell Lymphoma Cell Line

We noted with some anticipation a recent publication in this journal, describing the establishment of a novel mucosa-associated lymphoid tissue (MALT) lymphoma cell line, MA-1 (Kuo et al., 2011). To our knowledge, this would be the first cell line to be successfully established from gastric MALT lymphoma, an unusual extranodal form of B-cell lymphoma. MALT lymphoma has been extensively characterized over the last several decades, but further discoveries are hampered by lack of access to appropriate in vitro models for the disorder (Du, 2007). Our anticipation was tempered, however, by the knowledge that novel cell lines often do not match up to expectations because of crosscontamination and misidentification. Cultures being handled for prolonged periods—for example, during cell line establishment—can easily be cross-contaminated if cells from another culture are introduced by accident (Capes-Davis et al., 2013). The original culture is almost always overgrown by the imposter cell line, often without the scientist at the microscope being aware of the change. The end result is a misidentified cell line, and a series of publications that relate to the imposter rather than the original tissue, cell type or disease state. Cell line cross-contamination and misidentification are not new. Publications dating from the 1960s to the present day (Masters et al., 2012) have urged the scientific community to thoroughly characterize novel cell lines, and authenticate cell line stocks used in experimental work. Recently, however, a sustained effort has been made to standardize the methods used to authenticate human cell lines. Short tandem repeat (STR) profiling is now accepted as an effective way to authenticate human cell lines. A Standard has been published by the American National Standards Institute (ANSI), giving protocols and guidelines for STR profiling as applied to cell lines (ANSI/ATCC ASN-0002–2011, 2012). The International Cell Line Authentication Committee (ICLAC) was established following publication of the Standard to increase awareness and provide resources to help address these ongoing problems (Masters et al., 2012). The MA-1 cell line was analyzed using STR profiling, and its STR profile was published as part of its characterization (Kuo et al., 2011). However, for a cell line to be authenticated, there is a requirement to compare that profile to another sample—preferably from the same donor. Online databases have been developed to allow comparison to other commonly used cell lines, with results made available for this purpose by cell line repositories worldwide (Dirks et al., 2010). An STR profile for the donor of MA-1 was not made available (Kuo et al., 2011), so we compared the cell line result to several STR profile databases (Dirks et al., 2010). A match was found to the Pfeiffer cell line, held by the American Type Culture Collection (ATCC) and established in 1992 from a patient with nonHodgkin lymphoma (Gabay et al., 1999). Comparison of the two STR profiles shows 100% match across eight core STR loci and the gender marker amelogenin (Table 1). These loci have been shown to unequivocally authenticate 98% of cell line samples when assessed using a dataset of 2,279 samples from four cell banks (Capes-Davis et al., 2013). The MA-1 cell line was subsequently obtained from the authors and retested at the Leibniz Institute German Collection of Microorganisms and Cell Cultures (DSMZ) with identical results. Unless further stock can be found that corresponds to the original donor, we must conclude that the MA-1 cell line is misidentified and cannot be used as a model for MALT lymphoma. Laboratories and cell line repositories worldwide are working to characterize existing cell lines, focusing on authentication and diseasespecific markers and mutations (Ottaviano et al., 2010). This task is made more difficult by lack of