title: Characterization of a case of follicular lymphoma transformed into B-lymphoblastic leukemia.
abstract: Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with an ability to transform into a more aggressive disease, albeit infrequently to B-lymphoblastic leukemia/lymphoma. While t(14;18)(q32;q21) has been associated with approximately 90% cases of FL, that alteration alone is insufficient to cause FL and associated mutations are still being elucidated. The transformation of FL to B-lymphoblastic leukemia generally includes the dysregulation of MYC gene expression, typically through IGH rearrangement. Such cases of "double-hit" leukemia/lymphoma with both BCL2 and MYC translocations warrant further study as they are often not identified early, are associated with a poor prognosis, and are incompletely understood in molecular terms. Here we describe a patient with a diagnosis of FL that transformed to B-lymphoblastic leukemia. Detailed cytogenetic characterization of the transformed specimen using karyotype, fluorescence in situ hybridization, microarray and gene rearrangement analyses revealed a complex karyotype comprised principally of whole chromosome or whole arm copy number gains or losses. Smaller, single-gene copy number alterations identified by microarray were limited in number, but included amplification of a truncated EP300 gene and alterations in NEIL1 and GPHN. Analyses defined the presence of an IGH/BCL2 fusion due to a translocation as well as a MYC/IGH fusion due to an insertion, with both rearrangements involving the same IGH allele. The data illustrate the value in characterizing double-hit lymphoma cases with both traditional and novel technologies in the detailed cytogenetic workup.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Signature Genomic Laboratories/Perkin Elmer, 2820 N Astor, Spokane, WA, 99207, USA.
authors.forename: Aubry
authors.initials: A
authors.lastname: Foss
authors.affiliation: Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Kimball
authors.affiliation: Signature Genomic Laboratories/Perkin Elmer, 2820 N Astor, Spokane, WA, 99207, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Neill
authors.affiliation: Signature Genomic Laboratories/Perkin Elmer, 2820 N Astor, Spokane, WA, 99207, USA.
authors.forename: Tricia
authors.initials: T
authors.lastname: Matz
authors.affiliation: Signature Genomic Laboratories/Perkin Elmer, 2820 N Astor, Spokane, WA, 99207, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Schultz