MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations

• Published in: European journal of haematology Vol. 92; no. 1; pp. 42 - 48
• Main Authors: Pedersen, Mette Ø., Gang, Anne O., Poulsen, Tim S., Knudsen, Helle, Lauritzen, Anne F., Nielsen, Signe L., Klausen, Tobias W., Nørgaard, Peter
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2014
• Subjects: Aged; Aged, 80 and over; BCL2 genes; chromosomal translocation; diffuse large B-cell lymphoma; double-hit; Genes, bcl-2; Genes, myc; Humans; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Male; Middle Aged; MYC genes; MYC translocation partner genes; Neoplasm Staging; Prognosis; Translocation, Genetic; MYC genes; BCL2 genes; diffuse large B-cell lymphoma; double-hit; MYC translocation partner genes; chromosomal translocation
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.12212

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 Flourescent 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.