title: Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab.
abstract: OBJECTIVE
  Rearrangement of MYC occurs in a proportion of diffuse large B-cell lymphomas (DLBCL), where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC translocations in DLBCL and their prognostic impact in the era of cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (CHOP-R) therapy.
  
  
  METHODS
  Three hundred three patients with previously untreated DLBCL, with no evidence of underlying follicular lymphoma, were investigated using immunohistochemistry and interphase fluorescent in situ hybridization for MYC, BCL6, and t(14;18)/BCL2 rearrangements. All patients (median age, 71.1 years; range, 23 to 96 years) were treated when CHOP-R was standard therapy for DLBCL and observed for a maximum of 4 years. Overall survival (OS) at 3 years was 49% (95% CI, 42% to 56%).
  
  
  RESULTS
  MYC rearrangements were demonstrated in 35 (14%) of 245 biopsies with data available. Of these, 26 (74%) also had a t(14;18), 10 (26%) were BCL6 and MYC rearranged, and seven had all three abnormalities. Only age, International Prognostic Index, and MYC rearrangement retained prognostic significance in the final model. OS was significantly worse for patients with rearrangement of MYC (survival probability at 2 years = 0.35 in v 0.61 in the nonrearranged group).
  
  
  CONCLUSIONS
  The presence of a MYC rearrangement is a strongly adverse prognostic factor in CHOP-R-treated patients and can be used in combination with patients' age and IPI to accurately predict clinical outcome. In DLBCL, rearrangement of MYC is rarely found as the sole genetic abnormality and the poor prognosis of these patients is likely to reflect a synergistic effect alongside deregulation of BCL6 or BCL2.
authors.affiliation: Haematology Malignancy Diagnostic Service (HMDS), St James's Institute of Oncology, Leeds, United Kingdom. sharonb@hmds.org.uk
authors.forename: Sharon
authors.initials: S
authors.lastname: Barrans
authors.forename: Simon
authors.initials: S
authors.lastname: Crouch
authors.forename: Alex
authors.initials: A
authors.lastname: Smith
authors.forename: Kathryn
authors.initials: K
authors.lastname: Turner
authors.forename: Roger
authors.initials: R
authors.lastname: Owen
authors.forename: Russell
authors.initials: R
authors.lastname: Patmore
authors.forename: Eve
authors.initials: E
authors.lastname: Roman
authors.forename: Andrew
authors.initials: A
authors.lastname: Jack
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab; D014178:Translocation, Genetic; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone