TY - JOUR
T1 - Evolving insights into the genomic complexity and immune landscape of diffuse large B-cell lymphoma
T2 - opportunities for novel biomarkers
AU - El Hussein, Siba
AU - Shaw, Kenna R.M.
AU - Vega, Francisco
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
PY - 2020/12
Y1 - 2020/12
N2 - Recently, comprehensive genomic analyses have allowed a better molecular characterization of diffuse large B-cell lymphoma (DLBCL), offering novel opportunities in patient risk stratification and management. In the era of precision medicine, this has allowed us to move closer toward a more promising therapeutic outcome in the setting of DLBCL. In this review, we highlight the newly reported heterogeneous mutational landscapes of DLBCL (from two whole-exome sequencing studies, and from a more recent work targeting a 293-gene of a hematologic malignancy-designed panel. Altogether, these studies provide further evidence of the clinical applicability of genomic tests. We also briefly review established biomarkers in DLBCL (e.g., MYC and TP53), and our understanding of the germinal center cell reaction, including its epigenetic regulation, emphasizing some of the key epigenetic modifiers that play a role in lymphomagenesis, with available therapeutic targets. In addition, we present current data regarding the role of immune landscapes in DLBCL (inflamed versus non-inflamed), how the recently defined molecular DLBCL subtypes may affect the cellular composition of the tumor microenvironment and the function of the immune cells, and how this new knowledge may result in promising therapeutic approaches in the near future.
AB - Recently, comprehensive genomic analyses have allowed a better molecular characterization of diffuse large B-cell lymphoma (DLBCL), offering novel opportunities in patient risk stratification and management. In the era of precision medicine, this has allowed us to move closer toward a more promising therapeutic outcome in the setting of DLBCL. In this review, we highlight the newly reported heterogeneous mutational landscapes of DLBCL (from two whole-exome sequencing studies, and from a more recent work targeting a 293-gene of a hematologic malignancy-designed panel. Altogether, these studies provide further evidence of the clinical applicability of genomic tests. We also briefly review established biomarkers in DLBCL (e.g., MYC and TP53), and our understanding of the germinal center cell reaction, including its epigenetic regulation, emphasizing some of the key epigenetic modifiers that play a role in lymphomagenesis, with available therapeutic targets. In addition, we present current data regarding the role of immune landscapes in DLBCL (inflamed versus non-inflamed), how the recently defined molecular DLBCL subtypes may affect the cellular composition of the tumor microenvironment and the function of the immune cells, and how this new knowledge may result in promising therapeutic approaches in the near future.
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U2 - 10.1038/s41379-020-0616-y
DO - 10.1038/s41379-020-0616-y
M3 - Review article
C2 - 32620919
AN - SCOPUS:85087485184
SN - 0893-3952
VL - 33
SP - 2422
EP - 2436
JO - Modern Pathology
JF - Modern Pathology
IS - 12
ER -