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Incorporation of digital gene expression profiling for cell-of-origin determination (Lymph2Cx testing) into the routine work-up of diffuse large B cell lymphoma

  • Ryan S. RobetoryeEmail author
  • Colleen A. Ramsower
  • Allison C. Rosenthal
  • Tameson K. Yip
  • Amy J. Wendel Spiczka
  • Betty J. Glinsmann-Gibson
  • Lisa M. Rimsza
Original Article

Abstract

Diffuse large B cell lymphomas (DLBCL) represent a clinically heterogeneous group of lymphomas that are classified together based on similarities in morphology and immunophenotype. Gene expression profiling further classifies DLBCL into distinct molecular subgroups based on cell-of-origin (COO), including germinal center B cell type, activated B cell type, and unclassified type. COO assignment of DLBCL has important biological and prognostic significance, as well as emerging therapeutic implications. Herein, we describe the first clinical validation of a digital gene expression-profiling assay (Lymph2Cx) to perform COO assignment in the routine work-up of DLBCL using formalin-fixed paraffin-embedded (FFPE) tissue sections and describe the results of 90 consecutive DLBCL cases analyzed prospectively by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified clinical molecular diagnostics laboratory.

Keywords

Diffuse large B cell lymphoma Cell-of-origin Lymph2Cx Gene expression profiling 

Notes

Acknowledgments

Lymphoma and Leukemia Molecular Profiling Project for the science behind the Lymph2Cx assay. Center for Individualized Medicine, Mayo Clinic for support of the Molecular Diagnostics Arizona Laboratory. Lymphoma Oncologists and Hematopathologists of the Mayo Clinic in Rochester, MN, Jacksonville, FL, and Phoenix, AZ for contribution of clinical cases.

Authors’ contributions

R.S.R. and L.M.R.: conception, design, data analysis and interpretation, and manuscript editing

C.A.R.: assay design and performance, statistical calculations, and manuscript editing

A.C.R.: case identification and submission and manuscript editing

T.K.Y.: assay performance and manuscript editing

A.J.W.S., B.J.G-G.: assay design and performance and manuscript editing

Funding information

L.M.R. received funding from the Molecular Diagnosis and Prognosis in Aggressive Lymphomas, National Cancer Institute Grant #U01CA57581.

Compliance with ethical standards

This study was performed with Mayo Clinic Arizona Institutional Review Board approval under protocol #17-006519.

Conflicts of interest

MDAZL: Center for Individualized Medicine, Mayo Clinic.

L.M.R. is a co-inventor on a patent for the NanoString technology used in this manuscript but has received no licensing fees or royalty payments.

Other authors declare that they have no conflict of interest.

Supplementary material

12308_2019_344_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 22 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Molecular Diagnostics Laboratory Arizona (MDAZL), Department of Laboratory Medicine and Pathology, Mayo Clinic in ArizonaMayo Clinic HospitalPhoenixUSA
  2. 2.Division of Hematology and Oncology, Department of Internal MedicineMayo Clinic in ArizonaPhoenixUSA

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