Clinical laboratory validation of the MCL35 assay for molecular risk stratification of mantle cell lymphoma
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ORIGINAL ARTICLE
Clinical laboratory validation of the MCL35 assay for molecular risk stratification of mantle cell lymphoma Colleen A. Ramsower 1 & Alanna Maguire 2 & Ryan S. Robetorye 1 & Andrew L. Feldman 3 & Sergei I. Syrbu 4 & Allison C. Rosenthal 5 & Lisa M. Rimsza 1 Received: 24 August 2020 / Accepted: 29 September 2020 # The Author(s) 2020
Abstract Mantle cell lymphoma (MCL) is a clinically heterogeneous B cell malignancy for which a variety of prognostic factors have been proposed. Previously, a digital gene expression profiling “proliferation signature” capable of risk stratifying MCL was identified and subsequently developed into a multi-analyte prognostic assay, known as the “MCL35” assay. In this study, we sought to explore the performance characteristics of the MCL35 assay in a clinical laboratory and compare results with the Ki67 proliferation marker. The results describe the clinical validation of the MCL35 assay for molecular risk stratification of MCL including accuracy, sensitivity, specificity, use in acid-decalcified bone marrow core biopsies, fixatives, lower limit of RNA input, quality metrics, and other laboratory parameters. The resulting data indicate that this is a robust technique with outstanding reproducibility. Overall, the data support the concept of molecular signatures, as assessed with digital gene expression profiling, for improved standardization and reproducibility for proliferation assessment in MCL. Keywords Mantle cell lymphoma . Gene expression profiling . Ki67 . Prognosis
Introduction Mantle cell lymphoma (MCL) is a B cell malignancy that accounts for 2–6% of all non-Hodgkin B cell malignancies and is recognized by the World Health Organization (WHO) as a unique entity whose optimal clinical management is evolving [1]. With rare exceptions, MCL is characterized by a chromosomal translocation at t(11;14)(q13;q32) that Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12308-020-00418-4) contains supplementary material, which is available to authorized users. * Lisa M. Rimsza [email protected] 1
Department of Laboratory Medicine & Pathology, Mayo Clinic Arizona, 13400 E. Shea Blvd, CRB1-263, Scottsdale, AZ 85259, USA
2
Department of Research, Mayo Clinic Arizona, Scottsdale, AZ, USA
3
Department of Laboratory Medicine and Pathology, Mayo Clinic Minnesota, Rochester, MN, USA
4
Department of Pathology, University of Iowa, Iowa City, IA, USA
5
Internal Medicine, Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA
relocates the CCND1 gene from its position at 11q13 to 14q32, placing it adjacent to the highly transcribed immunoglobulin heavy chain gene (IGH), resulting in overexpression of Cyclin D1, the downstream protein product of CCND1, and a potent driver of cell proliferation [2]. Further underscoring the importance of Cyclin D1 and proliferation in MCL, point mutations and genomic deletions in CCND1 resulting in more stable Cyclin D1 transcripts with extended half-lives are associated with re
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