Details

Autor(en) / Beteiligte

• Ennishi, Daisuke
• Mottok, Anja
• Ben-Neriah, Susana
• Shulha, Hennady P.
• Farinha, Pedro
• Chan, Fong Chun
• Meissner, Barbara
• Boyle, Merrill
• Hother, Christoffer
• Kridel, Robert
• Lai, Daniel
• Saberi, Saeed
• Bashashati, Ali
• Shah, Sohrab P.
• Morin, Ryan D.
• Marra, Marco A.
• Savage, Kerry J.
• Sehn, Laurie H.
• Steidl, Christian
• Connors, Joseph M.
• Gascoyne, Randy D.
• Scott, David W.

Titel

Genetic profiling of MYC and BCL2 in diffuse large B-cell lymphoma determines cell-of-origin–specific clinical impact

Ist Teil von

• Blood, 2017-05, Vol.129 (20), p.2760-2770

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• The clinical significance of MYC and BCL2 genetic alterations in diffuse large B-cell lymphoma (DLBCL), apart from translocations, has not been comprehensively investigated using high-resolution genetic assays. In this study, we profiled MYC and BCL2 genetic alterations using next-generation sequencing and high-resolution SNP array in 347 de novo DLBCL cases treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) at the British Columbia Cancer Agency. Cell-of-origin (COO) subtype was determined by Lymph2Cx digital gene expression profiling. We showed that the incidence of MYC/BCL2 genetic alterations and their clinical significance were largely dependent on COO subtypes. It is noteworthy that the presence of BCL2 gain/amplification is significantly associated with poor outcome in activated B-cell-like and BCL2 translocation with poor outcome in germinal center B-cell subtypes, respectively. Both have prognostic significance independent of MYC/BCL2 dual expression and the International Prognostic Index (IPI). Furthermore, the combination of BCL2 genetic alterations with IPI identifies markedly worse prognostic groups within individual COO subtypes. Thus, high-resolution genomic assays identify extremely poor prognostic groups within each COO subtype on the basis of BCL2 genetic status in this large, uniformly R-CHOP-treated population-based cohort of DLBCL. These results suggest COO subtype-specific biomarkers based on BCL2 genetic alterations can be used to risk-stratify patients with DLBCL treated with immunochemotherapy. •MYC and BCL2 genetic alterations are associated with COO subtype-specific clinical effect in R-CHOP-treated DLBCL.