domingo, 9 de abril de 2017

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

2017 Mar 28. pii: blood-2016-11-747022. doi: 10.1182/blood-2016-11-747022. [Epub ahead of print]

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

Ennishi D1, Mottok A1, Ben-Neriah S1, Shulha HP1, Farinha P1, Chan FC1, Meissner B1, Boyle M1, Hother C1, Kridel R1, Lai D2, Saberi S2, Bashashati A2, Shah SP2, Morin RD3, Marra MA3, Savage KJ1, Sehn LH1, Steidl C1, Connors JM1, Gascoyne RD1, Scott DW4.

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Abstract

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. Noteworthy, the presence of BCL2 gain/amplification is significantly associated with poor outcome in Activated B-Cell-like (ABC) and BCL2 translocation with poor outcome in Germinal Centre B-cell (GCB) 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 DLBCL patients treated with immunochemotherapy.