title: Spectral karyotyping identifies new rearrangements, translocations, and clinical associations in diffuse large B-cell lymphoma.
abstract: Diffuse large B-cell lymphoma (DLBCL), a histologically well-defined subset of non-Hodgkin lymphoma, is clinically and genetically heterogenous. By G-banding, most cases showed complex hyperdiploid karyotypes and diverse cytogenetic abnormalities that included recurring and nonrecurring translocations, deletions, duplications, and marker chromosomes. While G-banding provided valuable leads to identification of specific rearrangements that enabled gene discovery and clinical correlations, many aberrations remained uncharacterized because of their complexity. The molecular cytogenetic technique spectral karyotyping (SKY), on the other hand, enables complete characterization of all aberrations in a tumor cell karyotype and, hence, precise quantitation of chromosome instability. We report here, for the first time, SKY analysis of a panel of 46 DLBCL cases previously analyzed by G-banding, ascertained at the Memorial Sloan-Kettering Cancer Center. This analysis provided a cytogenetic profile of DLBCL that was characterized by a higher level of instability, qualitatively as well as quantitatively, compared with G-banding. Thus, 551 breakpoints were detected by SKY, in contrast to the 295 by G-banding. Several new recurring breakpoints, translocations, and regions of gain and loss were identified, which included 13 breakpoints not previously identified by G-banding, 10 breakpoints that were underrepresented by G-banding, and 4 previously unrecognized translocations: der(14)t(3;14)(q21;q32), t(1;13)(p32;q14), t(1;7)(q21;q22), and der(6)t(6;8)(q11;q11). We identified new clinical associations involving recurring breakpoints detected by SKY. These studies emphasize the value of SKY analysis for redefinition of chromosomal instability in DLBCL to enhance gene discovery as well as clinical correlation analysis.
authors.affiliation: Cell Biology Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Gouri
authors.initials: G
authors.lastname: Nanjangud
authors.forename: Pulivarthi H
authors.initials: PH
authors.lastname: Rao
authors.forename: Abhijith
authors.initials: A
authors.lastname: Hegde
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Gerard
authors.initials: G
authors.lastname: Donnelly
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Jhanwar
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: R S K
authors.initials: RS
authors.lastname: Chaganti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D005260:Female; D015321:Gene Rearrangement; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic
chemical_list: D005819:Genetic Markers