Anaplastic Large Cell Lymphoma (ALCL) is a clinical and biological heterogeneous disease including systemic ALK positive and ALK negative entities. To discover biomarkers and/or genes involved in ALK negative ALCL pathogenesis, we applied the Cancer Outlier Profile Analysis (COPA) algorithm to a gene expression profiling data set including 249 cases of T-cell non-Hodgkin lymphoma and normal T-cells. Ectopic co-expression of ERBB4 and COL29A1 genes was detected in 24% of ALK negative ALCL patients. RNA sequencing and 5'RNA Ligase-Mediated Rapid Amplification of cDNA Ends (RLM-RACE) identified two novel ERBB4 truncated transcripts, displaying intronic Transcription Start Sites. By luciferase assays we defined that the expression of ERBB4 aberrant transcripts is promoted by endogenous intronic Long Terminal Repeats (LTRs). ERBB4 expression was confirmed at protein level by western blotting and immunohistochemistry. Finally, we demonstrated that the expression of ERBB4 truncated forms show oncogenic potentials and that ERBB4 pharmacological inhibition partially controls ALCL cell growth and disease progression in an ERBB4 positive patient-derived tumorgraft model. In conclusion, we identified a new subclass of ALK negative ALCL characterized by aberrant expression of ERBB4 truncated transcripts carrying intronic 5'UTRs.

Identification of a new subclass of ALK negative ALCL expressing aberrant levels of ERBB4 transcripts

SCARFO', IRENE;PELLEGRINO, Elisa;MEREU, ELISABETTA;BERGAGGIO, ELISA;GARAFFO, GIULIA;VITALE, NICOLETTA;CIRCOSTA, Paola;BARRECA, Antonella;SERRA, SARA;DEAGLIO, Silvia;INGHIRAMI, Giorgio;PIVA, Roberto
Last
2016-01-01

Abstract

Anaplastic Large Cell Lymphoma (ALCL) is a clinical and biological heterogeneous disease including systemic ALK positive and ALK negative entities. To discover biomarkers and/or genes involved in ALK negative ALCL pathogenesis, we applied the Cancer Outlier Profile Analysis (COPA) algorithm to a gene expression profiling data set including 249 cases of T-cell non-Hodgkin lymphoma and normal T-cells. Ectopic co-expression of ERBB4 and COL29A1 genes was detected in 24% of ALK negative ALCL patients. RNA sequencing and 5'RNA Ligase-Mediated Rapid Amplification of cDNA Ends (RLM-RACE) identified two novel ERBB4 truncated transcripts, displaying intronic Transcription Start Sites. By luciferase assays we defined that the expression of ERBB4 aberrant transcripts is promoted by endogenous intronic Long Terminal Repeats (LTRs). ERBB4 expression was confirmed at protein level by western blotting and immunohistochemistry. Finally, we demonstrated that the expression of ERBB4 truncated forms show oncogenic potentials and that ERBB4 pharmacological inhibition partially controls ALCL cell growth and disease progression in an ERBB4 positive patient-derived tumorgraft model. In conclusion, we identified a new subclass of ALK negative ALCL characterized by aberrant expression of ERBB4 truncated transcripts carrying intronic 5'UTRs.
2016
14
127
221
232
https://www.sciencedirect.com/science/article/pii/S0006497120305619?via=ihub
Scarfo', Irene; Pellegrino, Elisa; Mereu, Elisabetta; Kwee, Ivo; Agnelli, Luca; Bergaggio, Elisa; Garaffo, Giulia; Vitale, Nicoletta; Caputo, Manuel; ...espandi
File in questo prodotto:
File Dimensione Formato  
221.full.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 2.43 MB
Formato Adobe PDF
2.43 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1531650
Citazioni
  • ???jsp.display-item.citation.pmc??? 40
  • Scopus 89
  • ???jsp.display-item.citation.isi??? 89
social impact