title: Karyotypic abnormalities associated with Epstein-Barr virus status in classical Hodgkin lymphoma.
abstract: Classical Hodgkin lymphoma (CHL) is morphologically characterized by scattered malignant Hodgkin/Reed-Sternberg (HRS) cells that are far outnumbered by surrounding reactive hematolymphoid cells. Approximately half of all cases of CHL are associated with infection by Epstein-Barr virus (EBV), an oncogenic herpesvirus that expresses a number of proteins thought to contribute to transformation. While a small number of published studies have attempted to identify recurrent cytogenetic abnormalities in CHL, no large case series have explored karyotypic differences between EBV-positive and EBV-negative tumors. Here, we report a two-institution retrospective investigation of cytogenetic features characterizing CHL. In our cohort, cases of EBV-negative CHL were characterized by more complex routine karyotypes than their EBV-positive counterparts (24.6 versus 15.6 independent aberrations per case, P = 0.009). The increased complexity of EBV-negative cases was driven by a number of features suggestive of genomic instability, including a larger number of independent chromosomal breakpoints (P = 0.03) and apparently aneuploid autosomes (P = 0.008). Compelling but nonsignificant trends also suggest a larger modal number and increased marker chromosomes in EBV-negative cases (P = 0.13 and 0.06, respectively). While some of these differences are related to histologic subtype, others appear independent of histology. Finally, a significant subset of EBV-positive tumors has a surprisingly simple karyotype relative to what is normally seen in CHL, an observation suggesting considerable biological and genetic diversity in this disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: nathan.montgomery@unchealth.unc.edu.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Montgomery
authors.affiliation: McClendon Clinical Laboratories, UNC Hospitals, Chapel Hill, NC, USA.
authors.forename: Wilborn B
authors.initials: WB
authors.lastname: Coward
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Department of Pathology, The University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gulley
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Mathews
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Pediatrics, The University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kaiser-Rogers
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Pediatrics, The University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Rao
authors.affiliation: Human Genetics Laboratory, Munroe-Meyer Institute, The University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
authors.affiliation: Human Genetics Laboratory, Munroe-Meyer Institute, The University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Sanmann
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fedoriw
mesh_terms: D004854:Herpesvirus 4, Human / Q000502:physiology*; D006689:Hodgkin Disease / Q000235:genetics / Q000821:virology*; D006801:Humans; D007621:Karyotyping
keywords: Classical Hodgkin lymphoma; Epstein–Barr virus; genomic instability; karyotype