WARNING: G‐401 and SK‐NEP‐1 cell lines are not Wilms tumor cell lines

Scientific knowledge and progress, as well as human knowledge, relies on history and starts from history. We study literature on the subject of interest, and we start to imagine and plan our work from available, published data. Thus, a necessary prerequisite for our studies to add new knowledge is to have a solid, trusted base of prior knowledge to build on. Cell lines are easily accessible resources and important models for life science research. Cancer research relies on cell lines as effective models for the cell type and for the pathology being studied. However, the use of cell lines requires a lot of caution. First of all, correct assignment of diagnosis to the cell line used as model is necessary. If the patient from whom the line was initially derived was given a diagnosis different from that which would be made nowadays, cell line origin should be corrected accordingly. Furthermore, an emerging problem is that of cell linemisidentification, which refers to a cell line no longer corresponding to the donor or species fromwhich it was originally established. This is the object of cell line authentication, promoted by the International Cell Line Authentication Committee (ICLAC, https://iclac.org/). 1 It is necessary to picture the consequences that studiesperformedon “wrong” cell lines canhave in termsof adding misinformation to the literature, potentially generating further studies that lead to other misleading data, not to mention the waste of economical and intellectual resources. An accurate estimate has been performed and its findings are disturbing.2 Nevertheless, not all published data obtained by the use of “wrong” lines should be considered useless. For example, if themistake lies in a different diagnosis, the correct attribution of the findings to the right pathology can retain the value of the previous efforts made by researchers. In pediatric oncology, which represents only 0.5%of all cancers, the rarity of patients, togetherwith the small number of researchers involved in the fieldworldwide, and of the corresponding research grants, make any published paper important. This is what prompted us to write this warning. With this communication, we intend to clarify once and for all that G-401 and SK-NEP-1 are not Wilms tumor cell lines, and thus, studies performed with them cannot be claimed as Wilms tumors studies. The need for this statement comes from the fact that even now, 26 and 13 years after their identification as being derived from nonWilms tumors, respectively, somepapersusing these cell lines asWilms tumor models are still being published and reported in PubMed. This means that some researchers, reviewers, and editors are not aware of the fact that, although both cell lines were initially classified as Wilms tumor cell lines, evidence demonstrating corrected lineage has been published subsequently.3,4 We will briefly recall the facts that led to classify G-401 as a rhabdoid tumor of the kidney,3 and SK-NEP-1 as a Ewing sarcoma cell line.4 The G-401 cell line was established in 1975 by a NIH fellow, Dr. P.T. Peebles, from a kidney tumor, classified at that time as Wilms tumor, surgically resected from a 3-month-old male child who eventually died.3 It has to be remembered that 1975 was before the completion of the first National Wilms tumor study,5 and that other renal neoplasias, such as the entities clear cell sarcoma of kidney and malignant rhabdoid tumor of the kidney, were classified as Wilms tumor variants. The establishment of the G-401 cell line is reported in abstract form only,6 and when Dr. A.J. Garvin and colleagues tried to locate the original tumor tissue blocks and hospital of origin, they failed.3 Then, they used the G-401 cell line obtained from the American Type Culture Collection (ATCC) to inject nude mice and obtain tumor tissue to investigate. The evidence they collected are those obtainable in the 1990s, thus they are based on histology, ultrastructure, immunohistochemical, and RNA analyses that compared the heterotransplants derived from the G-401 cell line with those derived fromWilms tumor and rhabdoid tumor of the kidney, and led them to conclude that the G-401 cell line derives from a rhabdoid tumor of the kidney.3 Very importantly, examination of the G-401-obtained tumor tissue by local pathologists and byDr. BruceBeckwith, director of theNationalWilms tumor Study, “yielded complete agreement that the tumor did not resemble a Wilms, but resembled a rhabdoid tumor of the kidney”. 3