APPLICATION OF INTERPHASE CYTOGENETICS FOR THE DETECTION OF T(11-14)(Q13-Q32) IN MANTLE CELL LYMPHOMAS

Background: The chromosomal translocation t(11;14)(q13;q32) is the hal lmark of mantle cell lymphoma (MCL) in which it can be detected cytoge netically 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 chr omosome band 14q32 and, thus, leads to deregulation of the cell cycle regulatory protein cyclin D1, which is encoded by the CCND1 gene local ized at the telomeric border of the bcl-1-locus. MCL has the worst pro gnosis of all low-grade non-Hodgkin's lymphomas (NHL). In some instanc es, however, histopathologic differentiation between MCL and other low -grade B-cell NHL is difficult. Therefore, detection of the t(11;14) t ranslocation is of essential diagnostic value for the risk-adjusted ma nagement 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. Pa tients and methods. We established an interphase fluorescence in situ hybridization (FISH) approach for the detection of the t(11,14) transl ocation by use of a cosmid probe hybridizing to the IgH constant regio n and a YAC spanning the bcl-1 region. Cells containing a t(11;14) tra nslocation show a colocalisation of the signals for IgH and bcl-1. Eig ht control samples and 15 MCL specimens were investigated. Results: Ac cording to our control studies, samples containing more than 10% of ce lls with this signal constellation can be diagnosed as carrying a clon al 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 as say reliably detects the t(11;14) translocation irrespective of the lo cation of the breakpoints within the bcl-1 region. Conclusions: The de scribed interphase FISH assay provides a reliable and routinely applic able tool for diagnosis of the t(11;14) translocation.