title: The EML4-ALK transcript but not the fusion protein can be expressed in reactive and neoplastic lymphoid tissues.
abstract: Rearrangements involving the ALK gene define two distinct entities in the new 2008 WHO classification of lymphoid neoplasms, i.e. ALK+ anaplastic large cell lymphoma and a rare subset of ALK+ diffuse large B-cell lymphoma. Recently, rearrangements involving ALK and the echinoderm microtubule associated protein-like 4 (EML4) gene were described as a specific genetic alteration in about 6% of non-small cell lung cancer (NSCLC). We investigated the expression of EML4-ALK mRNA and protein in 51 reactive and 58 neoplastic lymphoid tissues. EML4-ALK transcripts were detected in 3/51 (5.9%) of reactive lymphoid tissues and 12/58 (20.7%) of lymphomas of different categories, including follicular lymphoma, diffuse large B-cell lymphoma and Hodgkin's disease. Notably, none of these cases expressed the EML4-ALK fusion protein at Western blotting samples and immunohistochemistry. These results indicate that EML4-ALK rearrangements are not specific of NSCLC and raise yet unsolved questions about their role in promoting human neoplasms.
authors.affiliation: Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Martelli
authors.forename: Davide
authors.initials: D
authors.lastname: Conte
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Modena
authors.forename: Valentina
authors.initials: V
authors.lastname: Pettirossi
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion