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

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.

Keywords: CHP-100; EWSR1-FLI1 translocation; Ewing family of tumors; Ewing's sarcoma (ES); cross-contamination; misclassification; neuroblastoma (NB); t(11;22)(q24;q12).