Cross contamination meets misclassification: Awakening of CHP ‐100 from sleeping beauty sleep—A reviewed model for Ewing's sarcoma

Abstract

Abstract A human cell line of neuroblastic tissue, which was believed to have been lost to science due to its unavailability in public repositories, is revived and reclassified. In the 1970s, a triple set of neuroblastoma (NB) cell lines became available for research as MYCN ‐amplified vs nonamplified models (CHP‐126/‐134 and CHP‐100, respectively). Confusingly, CHP‐100 was used in subsequent years as a model for NB and, since the 1990s, as a model for neuroepithelioma and later as a model for Ewing's sarcoma (ES), which inevitably led to non‐reproducible results. A deposit at a bioresource center revealed that globally available stocks of CHP‐100 were identical to the prominent NB cell line IMR‐32 and CHP‐100 was included into the list of misidentified cell lines. Now we report on the rediscovery of an authentic CHP‐100 cell line and provide evidence of incorrect classification during establishment. We show that CHP‐100 cells carry a t(11;22)(q24;q12) type II EWSR1‐FLI1 fusion and identify it as a classic ES. Although the question of whether CHP‐100 was a virtual and never existing cell line from the beginning is now clarified, the results of all relevant publications should be considered questionable. Neither the time of the cross‐contamination event with IMR‐32 is known nor was the final classification as a model for Ewing family of tumors available with an associated short tandem repeat profile. After a long road of errors and confusion, authentic CHP‐100 is now characterized as a type II EWSR1‐FLI1 fusion model 44 years after its establishment.

What's new? Cell lines from neuroblastoma and Ewing's sarcoma entities are vital disease modeling tools. In particular, cell line CHP‐100, established in the 1970s, has served as a non‐MYCN‐amplified neuroblastoma model. Global stocks of CHP‐100, however, may be identical to neuroblastoma cell line IMR‐32. Adding to the confusion, CHP‐100 has been used to study Ewing's sarcoma. Here, the authors report the rediscovery of an authentic CHP‐100 cell line, with evidence of a fusion gene that identifies the cells as classic Ewing's sarcoma. The findings suggest that CHP‐100 was incorrectly classified during establishment.