title: LMO2-negative Expression Predicts the Presence of MYC Translocations in Aggressive B-Cell Lymphomas.
abstract: MYC translocation is a defining feature of Burkitt lymphoma (BL), and the new category of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 translocations, and occurs in 6% to 15% of diffuse large B-cell lymphomas (DLBCLs). The low incidence of MYC translocations in DLBCL makes the genetic study of all these lymphomas cumbersome. Strategies based on an initial immunophenotypic screening to select cases with a high probability of carrying the translocation may be useful. LMO2 is a germinal center marker expressed in most lymphomas originated in these cells. Mining gene expression profiling studies, we observed LMO2 downregulation in BL and large B-cell lymphoma (LBCL) with MYC translocations, and postulated that LMO2 protein expression could assist to identify such cases. We analyzed LMO2 protein expression in 46 BLs and 284 LBCL. LMO2 was expressed in 1/46 (2%) BL cases, 146/268 (54.5%) DLBCL cases, and 2/16 (12.5%) high-grade B-cell lymphoma cases with MYC and BCL2 and/or BCL6 translocations. All BLs carried MYC translocation (P<0.001), whereas LMO2 was only positive in 6/42 (14%) LBCL with MYC translocation (P<0.001). The relationship between LMO2 negativity and MYC translocation was further analyzed in different subsets of tumors according to CD10 expression and cell of origin. Lack of LMO2 expression was associated with the detection of MYC translocations with high sensitivity (87%), specificity (87%), positive predictive value and negative predictive value (74% and 94%, respectively), and accuracy (87%) in CD10 LBCL. Comparing LMO2 and MYC protein expression, all statistic measures of performance of LMO2 surpassed MYC in CD10 LBCL. These findings suggest that LMO2 loss may be a good predictor for the presence of MYC translocation in CD10 LBCL.
authors.affiliation: *Department of Pathology, Hematopathology Unit, Hospital del Mar, Institute of Investigacions Mediques-IMIM, University Pompeu Fabra †Department of Pathology, Hematopathology Section, Hospital Clinic, Institute of Investigacions Biomediques Agust Pi Sunyer (IDIBAPS), University of Barcelona ‡Department of Pathology, Hospital de Bellvitge-IDIBELL, Hospitalet de Llobregat ¶Department of Pathology, Hospital de Sant Pau #Microarray Analysis Service, Institute of Investigacions Mediques-IMIM, Barcelona §Department of Pathology, Hospital Germans Trias i Pujol, Badalona ∥Department of Pathology, Hospital Mutua Terrassa, Terrassa, Spain **Institute of Pathology, Locarno, Switzerland.
authors.forename: Luis
authors.initials: L
authors.lastname: Colomo
authors.forename: Ivonne
authors.initials: I
authors.lastname: Vazquez
authors.forename: Natalia
authors.initials: N
authors.lastname: Papaleo
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrer
authors.forename: Catalina
authors.initials: C
authors.lastname: Franco
authors.forename: Laura
authors.initials: L
authors.lastname: Comerma
authors.forename: Silvia
authors.initials: S
authors.lastname: Hernandez
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvo
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.forename: Fina
authors.initials: F
authors.lastname: Climent
authors.forename: José Luis
authors.initials: JL
authors.lastname: Mate
authors.forename: Pilar
authors.initials: P
authors.lastname: Forcada
authors.forename: Anna
authors.initials: A
authors.lastname: Mozos
authors.forename: Lara
authors.initials: L
authors.lastname: Nonell
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.forename: Anna
authors.initials: A
authors.lastname: Carrio
authors.forename: Dolors
authors.initials: D
authors.lastname: Costa
authors.forename: Ivan
authors.initials: I
authors.lastname: Dlouhy
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Armando
authors.initials: A
authors.lastname: Lopez-Guillermo
authors.forename: Alexandra
authors.initials: A
authors.lastname: Valera
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D011518:Proto-Oncogene Proteins