TY - JOUR
T1 - Application of interphase cytogenetics for the detection of t(11;14)(q13;q32) in mantle cell lymphomas
AU - Siebert, R.
AU - Matthiesen, P.
AU - Harder, S.
AU - Zhang, Y.
AU - Borowski, A.
AU - Zühlke-Jenisch, R.
AU - Plendl, H.
AU - Metzke, S.
AU - Joos, S.
AU - Zucca, E.
AU - Weber-Matthiesen, K.
AU - Roggero, E.
AU - Grote, W.
AU - Schlegelberger, B.
N1 - Funding Information:
Supported by the Wilhelm-Sander-Stiftung (95.003.1) and the Deutsche Krebshilfe (10-0992-Schl3).
Funding Information:
Schilling-Stiftungsprofessur. E. Zucca was supported by the Schweizerische Krebsliga grant FOR 372. We thank Dr. Tsujimoto and Dr. Meeker for providing the bcl-\ probes. The authors are grateful to Prof. Dr. A. Feller (Department of Pathology, University of Liibeck, Germany) and Prof. Dr. H.-K. Miiller-Hermelink (Department of Pathology, University of Wiirzburg, Germany) for providing histopathologic diagnoses.
PY - 1998/5
Y1 - 1998/5
N2 - 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 hcl- 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.
AB - 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 hcl- 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.
KW - Cytogenetics
KW - Fluorescence in situ hybridization
KW - Mantle-cell lymphoma
KW - Translocation t(11;14)
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U2 - 10.1023/A:1008242729509
DO - 10.1023/A:1008242729509
M3 - Article
C2 - 9653493
AN - SCOPUS:7144228622
VL - 9
SP - 519
EP - 526
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 5
ER -