alexa Application of interphase cytogenetics for the detection of t(11;14)(q13;q32) in mantle cell lymphomas.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Siebert R, Matthiesen P, Harder S, Zhang Y, Borowski A,

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Abstract BACKGROUND: The chromosomal translocation t(11;14)(q13;q32) is the hallmark of mantle cell lymphoma (MCL) in which it can be detected cytogenetically in about 75\% of cases. The t(11;14) translocation juxtaposes the bcl-1 locus in chromosome band 11q13 next to the IgH locus in chromosome band 14q32 and, thus, leads to deregulation of the cell cycle regulatory protein cyclin D1, which is encoded by the CCND1 gene localized at the telomeric border of the bcl-1-locus. MCL has the worst prognosis of all low-grade non-Hodgkin's lymphomas (NHL). In some instances, however, histopathologic differentiation between MCL and other low-grade B-cell NHL is difficult. Therefore, detection of the t(11;14) translocation is of essential diagnostic value for the risk-adjusted management of patients with MCL. Unfortunately, chromosome analyses are frequently hampered by the low yield and quality of tumor metaphases. As the 11q13 breakpoints are scattered over a region of more than 120 kb the application of molecular genetic techniques is also limited. PATIENTS AND METHODS: We established an interphase fluorescence in situ hybridization (FISH) approach for the detection of the t(11;14) translocation by use of a cosmid probe hybridizing to the IgH constant region and a YAC spanning the bcl-1 region. Cells containing a t(11;14) translocation show a colocalisation of the signals for IgH and bcl-1. Eight control samples and 15 MCL specimens were investigated. RESULTS: According to our control studies, samples containing more than 10\% of cells with this signal constellation can be diagnosed as carrying a clonal t(11;14) translocation. All eleven MCL found to carry the t(11;14) translocation by chromosome analysis were positive in our FISH assay. Additionally, two of four MCL lacking a clonal t(11;14) translocation by chromosome analysis were shown to carry this aberration in 14\% and 37\% of interphase nuclei. Southern blot data indicate that our FISH assay reliably detects the t(11;14) translocation irrespective of the location of the breakpoints within the bcl-1 region. CONCLUSIONS: The described interphase FISH assay provides a reliable and routinely applicable tool for diagnosis of the t(11;14) translocation.
This article was published in Ann Oncol and referenced in Journal of Cytology & Histology

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