title: Molecular diagnosis in Ewing family tumors: the Rizzoli experience--222 consecutive cases in four years.
abstract: The Ewing's family of tumors (EFTs) are characterized by chimeric transcripts generated by specific chromosomal rearrangements. The most common fusions are between the EWSR1 gene on chromosome 22 and the ETS family of transcription factors; rarely, FUS (on chromosome 16) substitutes for EWSR1. The detection of specific translocations using molecular analysis is now a routine part of the pathological examination of EFT. Here, we report our experience with molecular diagnosis of EFT during the 4 years (2006-2009) at the Rizzoli Institute. We analyzed 222 consecutive tumors with a presumptive diagnosis of EFT using molecular techniques and IHC. We found five distinct types of EWSR1-FLI1 fusion transcripts resulting from translocation t(11;22), three types of EWSR1-ERG transcripts resulting from t(21;22), and one type of t(2;22) resulting in EWSR1-FEV fusion. Molecular investigation validated 92% of cases ultimately diagnosed as EFT; IHC validated 76% of the cases. Thus, despite the difficulties and limitations associated with both molecular and IHC analysis on fresh and formalin-fixed, paraffin-embedded tissue, a combination of these techniques is the best approach to enhancing the accuracy of EFT diagnosis. We also present our method for choosing which molecular techniques to apply. Finally, we collected the most prevalent breakpoints reported in the literature, indicating which exons are involved, the sequence breakpoints, and the NCBI reference sequences.
authors: Department of Pathology, Section of Molecular Biology, Rizzoli Institute, Via di Barbiano 1/10, Bologna, Italy. gabriella.gamberi@ior.it
authors: Gabriella
authors: G
authors: Gamberi
authors: Stefania
authors: S
authors: Cocchi
authors: Stefania
authors: S
authors: Benini
authors: Giovanna
authors: G
authors: Magagnoli
authors: Luca
authors: L
authors: Morandi
authors: Jennifer
authors: J
authors: Kreshak
authors: Marco
authors: M
authors: Gambarotti
authors: Piero
authors: P
authors: Picci
authors: Licciana
authors: L
authors: Zanella
authors: Marco
authors: M
authors: Alberghini
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001483:Base Sequence; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons; D005260:Female; D023061:Gene Order; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics; D012107:Research Design; D012512:Sarcoma, Ewing / Q000175:diagnosis* / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; C500986:EWSR1 protein, human; C474280:FEV protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG