title: MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations.
abstract: In large B-cell lymphoma (LBCL) MYC- and MYC/BCL2 double-hit (DH) translocations have been associated with inferior survival. We hypothesised that the negative prognostic impact of MYC translocation was determined by an immunoglobulin MYC translocation partner gene (IG-MYC), as opposed to a non-immunoglobulin partner gene (nonIG-MYC). In a prospective, unselected cohort of 237 LBCL patients MYC and BCL2 translocations were identified by fluorescent in situ hybridisation (FISH) with split probes. MYC translocation partner gene was identified by IGH/MYC fusion probes and/or kappa/lambda split probes. Clinical data were collected from patient files. MYC translocation was identified in 28/225 patients. IG-MYC translocation partner gene was identified in 12/24 patients. DH translocation was identified in 23/228 patients. IG-MYC translocation partner gene was identified in 9/19 DH patients. Neither MYC-nor DH translocation showed correlation with survival. However, MYC translocation with IG-MYC translocation partner gene was associated with worse OS compared with both MYC translocation with nonIG-MYC translocation partner gene (P = 0.02) as well as absence of MYC translocation (P = 0.03). In patients with DH a similar, however, stronger correlation was seen (P = 0.003 and P = 0.0004 respectively). MYC - or DH translocation with nonIG-MYC translocation partner gene was not associated with worse overall survival (P = 0.2 and P = 0.3 respectively). Most patients received Rituximab (86%) and CHOP/CHOP-like chemotherapy regimes (81%). We suggest that prognostic stratification of LBCL patients by MYC and/or DH translocations should include identification of MYC translocation partner gene because approximately half of the cases harbour nonIG-MYC translocation partner genes with no or minor influence on survival.
authors.affiliation: Department of Pathology, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Mette Ø
authors.initials: MØ
authors.lastname: Pedersen
authors.forename: Anne O
authors.initials: AO
authors.lastname: Gang
authors.forename: Tim S
authors.initials: TS
authors.lastname: Poulsen
authors.forename: Helle
authors.initials: H
authors.lastname: Knudsen
authors.forename: Anne F
authors.initials: AF
authors.lastname: Lauritzen
authors.forename: Signe L
authors.initials: SL
authors.lastname: Nielsen
authors.forename: Tobias W
authors.initials: TW
authors.lastname: Klausen
authors.forename: Peter
authors.initials: P
authors.lastname: Nørgaard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019254:Genes, bcl-2; D016259:Genes, myc; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D014178:Translocation, Genetic
keywords: BCL2 genes; MYC genes; MYC translocation partner genes; chromosomal translocation; diffuse large B-cell lymphoma; double-hit