ISSN:
1569-8041
Keywords:
cytogenetics
;
fluorescence in situ hybridization
;
mantle-cell lymphoma
;
translocation t(11;14)
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background: The chromosomal translocation t(11;14)(q13;q32) is thehallmark of mantle cell lymphoma (MCL) in which it can be detectedcytogenetically in about 75% of cases. The t(11;14) translocationjuxtaposes the bcl-1 locus in chromosome band 11q13 next to the IgH locus inchromosome band 14q32 and, thus, leads to deregulation of the cell cycleregulatory protein cyclin D1, which is encoded by the CCND1 gene localizedat the telomeric border of the bcl-1-locus. MCL has the worst prognosis ofall low-grade non-Hodgkin‘s lymphomas (NHL). In some instances, however,histopathologic differentiation between MCL and other low-grade B-cell NHLis difficult. Therefore, detection of the t(11;14) translocation is ofessential diagnostic value for the risk-adjusted management of patients withMCL. Unfortunately, chromosome analyses are frequently hampered by the lowyield and quality of tumor metaphases. As the 11q13 breakpoints arescattered over a region of more than 120 kb the application of moleculargenetic techniques is also limited. Patients and methods: We established an interphase fluorescence in situhybridization (FISH) approach for the detection of the t(11;14)translocation by use of a cosmid probe hybridizing to the IgH constantregion and a YAC spanning the bcl-1 region. Cells containing a t(11;14)translocation show a co-localisation of the signals for IgH and bcl-1. Eightcontrol samples and 15 MCL specimens were investigated. Results: According to our control studies, samples containing more than10% of cells with this signal constellation can be diagnosed ascarrying a clonal t(11;14) translocation. All eleven MCL found to carry thet(11;14) translocation by chromosome analysis were positive in our FISHassay. Additionally, two of four MCL lacking a clonal t(11;14) translocationby chromosome analysis were shown to carry this aberration in 14% and37% of interphase nuclei. Southern blot data indicate that our FISHassay reliably detects the t(11;14) translocation irrespective of thelocation of the breakpoints within the bcl-1 region. Conclusions: The described interphase FISH assay provides a reliable androutinely applicable tool for diagnosis of the t(11;14) translocation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008242729509
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