Elucidating the Gene Expression Signature of Rosai–Dorfman Disease: A Study from the Atlas of Blood Cancer Genomes Initiative
Year: 2026
Type: article
Study design: Observational Study
Abstract: Rosai-Dorfman disease (RDD) is a rare histiocytic disorder characterized by the accumulation of large histiocytes in nodal and/or extranodal sites. The underlying biology of RDD and factors that distinguish it from other histiocyte disorders are poorly understood. To better understand the disease biology, we employed whole-transcriptome RNA sequencing (RNA-seq) to study the gene expression profiles of RDD as part of the Atlas of Blood Cancer Genomes (ABCG) initiative. Gene expression profiles of RDD (N = 23) were then compared with two other histiocytoses [Langerhans cell histiocytosis (LCH; N = 15) and Erdheim-Chester disease (ECD; N = 4)], which are most often considered in the clinicopathologic differential diagnosis of RDD. We found that gene expression levels by RNA-seq correlated well with known immunohistochemistry results for diagnostic markers for all three diseases, highlighting the ability to use RNA-based approaches for the diagnosis of these tumors. RDD samples showed enrichment of gene sets related to B cells and the IL27 pathway. In contrast, LCH showed enrichment of gene sets related to resting dendritic cells and the HNF3A pathway. We found significant differences in the composition of the microenvironment, with an enrichment of memory B cells, plasma cells, and CD8 T cells in the RDD microenvironment and enrichment of dendritic cells in the LCH microenvironment. In summary, our study demonstrates unique gene expression signatures in RDD that show overlap as well as distinctive patterns from LCH or ECD. These novel gene expression signatures encompass pathways that could potentially contribute to the pathogenesis and targeted treatment of this rare histiocytic entity. SIGNIFICANCE: To our knowledge, this study is the first to report that protein expression of markers used in the immunohistochemical diagnosis of RDD and other histiocytoses correlates well with gene expression. This finding indicates that RNA-based methods can be used in the clinical diagnosis of RDD. We also demonstrate that RDD shows a unique tumor microenvironment that is rich in immune cells, including B cells, plasma cells, and CD8+ T cells.
Source: Cancer Research Communications
Authors: Sheren Younes, Fadzai Chinyengetere, Veronica Russell, Devang Thakkar, Emily F. Mason, Ridas Juskevicius, Alexandra E. Kovach, Shaoying Li, C. Cameron Yin, Dennis P. O’Malley, Jean L. Koff, David L. Jaye, Cassandra Love, Jennifer R. Shingleton, Dennis Owusu, Ayush Batra, Leonardo P.A. Biral, Elizabeth Thacker, Clay Parker, Lanie Happ, Jennifer Chapman Fredricks, Izidore S. Lossos, Sarah L. Ondrejka, Eric Hsi, Eric Tse, Rex K.H. Au-Yeung, Govind Bhagat, Rebecca J. Leeman-Neill, Amy Chadburn, Magdalena Czader, Yuri Fedoriw, Kikkeri N. Naresh, Sandeep S. Dave, Yasodha Natkunam
Institutions: Stanford University, Duke University, Vanderbilt University, Vanderbilt University Medical Center, The University of Texas MD Anderson Cancer Center, Emory University, Winship Cancer Institute, University of Miami, Sylvester Comprehensive Cancer Center, Cleveland Clinic, Mayo Clinic, University of Hong Kong, Saint Louis University, Columbia University Irving Medical Center, Weill Cornell Medicine, Weill Cornell Medical Center, Indiana University Indianapolis, Indiana University School of Medicine, University of North Carolina at Chapel Hill, Fred Hutch Cancer Center, Stanford Medicine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,550
OpenAlex ID: W7221551434