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Evidence-based review of genomic aberrations in diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS): Report from the cancer genomics consortium lymphoma working group

      Highlights

      • Clinical assessment of genetic alterations including structural variants, copy neutral loss of heterozygosity, and enriched pathogenic mutations through advanced technologies can enhance diagnostic and prognostic yield and guide therapeutic decisions in diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS).
      • The Cancer Genomics Consortium (CGC) Lymphoma Working Group reviewed the literature to evaluate genomic testing in the workup of DLBCL, NOS, the most common category of DLBCL, and surveyed current clinical practices.
      • This evidence-based review also includes a proposed testing approach aimed at maximizing the diagnostic yield for DLBCL, NOS.

      Abstract

      Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type of non-Hodgkin lymphoma (NHL). The 2016 World Health Organization (WHO) classification defined DLBCL, NOS and its subtypes based on clinical findings, morphology, immunophenotype, and genetics. However, even within the WHO subtypes, it is clear that additional clinical and genetic heterogeneity exists. Significant efforts have been focused on utilizing advanced genomic technologies to further subclassify DLBCL, NOS into clinically relevant subtypes. These efforts have led to the implementation of novel algorithms to support optimal risk-oriented therapy and improvement in the overall survival of DLBCL patients. We gathered an international group of experts to review the current literature on DLBCL, NOS, with respect to genomic aberrations and the role they may play in the diagnosis, prognosis and therapeutic decisions. We comprehensively surveyed clinical laboratory directors/professionals about their genetic testing practices for DLBCL, NOS. The survey results indicated that a variety of diagnostic approaches were being utilized and that there was an overwhelming interest in further standardization of routine genetic testing along with the incorporation of new genetic testing modalities to help guide a precision medicine approach. Additionally, we present a comprehensive literature summary on the most clinically relevant genomic aberrations in DLBCL, NOS. Based upon the survey results and literature review, we propose a standardized, tiered testing approach which will help laboratories optimize genomic testing in order to provide the maximum information to guide patient care.

      Keywords

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