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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2554-2561
NEOPLASIA
Spectral karyotyping identifies new rearrangements,
translocations, and clinical associations in diffuse large
B-cell lymphoma
Gouri Nanjangud,
Pulivarthi
H. Rao,
Abhijith Hegde,
Julie Teruya-Feldstein,
Gerard Donnelly,
Jing Qin,
Suresh C. Jhanwar,
Andrew D. Zelenetz, and
R. S. K. Chaganti
From the Cell Biology Program and the Departments of
Medicine, Pathology, and Epidemiology and Biostatistics, Memorial
Sloan-Kettering Cancer Center, New York, NY.
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.
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