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Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions

Holger Kohlhammer, Carsten Schwaenen, Swen Wessendorf, Karlheinz Holzmann, Hans A. Kestler, Dirk Kienle, Thomas F. E. Barth, Peter Möller, German Ott, Jörg Kalla, Bernhard Radlwimmer, Armin Pscherer, Stephan Stilgenbauer, Hartmut Döhner, Peter Lichter and Martin Bentz

Article Figures & Data

Figures

  • Figure 1.

    Clone selection of 812 BAC and PAC clones used for the MCL chip.

  • Figure 2.

    Summary of genomic aberrations detected by matrix-CGH in 53 cases of MCL. Lines to the left of the ideograms indicate loss of chromosomal material, and lines to the right indicate gain of chromosomal material. Black squares represent high-level DNA amplifications.

  • Figure 3.

    Comparison of matrix-CGH and CGH. The comparison of matrix-CGH (▪) and CGH (▦) in 45 cases of MCL is shown. The genomic aberrations are listed according to the affected chromosome arms. Genomic aberrations that were present in more than 5 cases are shown.

  • Figure 4.

    Delineation of consensus regions in MCL. BAC clones, the respective chromosomal band positions, and the physical localization in megabase pairs are listed for each of the clones. The genomic localization information is according to the NCBI database. Each square contains information on the genomic aberration status for a clone (rows) in the different cases (columns). White indicates no aberration; black, not evaluable; dark gray, genomic aberration of the respective clone (ratio value exceeds mean value ± 3 SD in comparison to a balanced set of clones); and light gray, trend toward genomic aberration (ratio value exceeds mean value ± 2 SD but not mean value ± 3 SD in comparison to a balanced set of clones). (A) Extension of 8p deletions in 18 MCLs. (B) Extension of 11q gains in 15 MCLs. (C) Extension of 11q deletions in 23 MCLs.

  • Figure 5.

    Minimal deleted region in band 13q14. The region between markers D13S165 and D13S25 and the relative positions of the BAC and PAC clones is shown. In addition, the positions of candidate genes in CLL and MCL and the minimal deleted regions defined in previous studies for CLL are illustrated (Bullrich et al,52 Kalachikov et al,53 Bouyge-Moreau et al,54 Corcoran et al,55 and Stilgenbauer et al56). In comparison to CLL, the consensus region in MCL, as defined by cases 13 and 52, is more centromeric.

Tables

  • Table 1.

    Patient characteristics

    Clinical featureNo. patientsAll patients evaluable for characteristic%
    Stage III/IV 37 40 92.5
    2 or more extranodal sites 24 34 70.6
    WHO performance status of 2 or more 6 30 20.0
    Leukemic 24 38 63.2
    LDH level elevated 10 31 32.3
    t(11;14)-positive 53 53 100.0
    CD5-positive 41 42 97.6
    CD19/CD20-positive 42 42 100.0
    CD23-negative 39 42 92.9
    • WHO indicates World Health Organization.

  • Table 2.

    Consensus regions in 53 patients with MCL

    Chromosomal bandMinimal segment of genomic gain/loss, MbpApproximate size, MbpNo. of casesCandidate genes
    –8p21 20.7-23.1 2.4 18 TNFRSF10B
    –9p21-9p22 14.3-26.5 12.2 19 CDKN2A, CDKN2B
    –10p14-10p15 0.0-12.4 12.4 11
    +10p13 22.1-24.8 2.7 6 BMI1
    +11q13 63.9-65.3 1.4 6 RELA, MAP4K2
    +11q13 66.5-71.7 5.2 6 CCND1, FGF3, FGF4
    –11q22-11q23 108.0-109.7 1.7 23 ATM, DDX10
    +11q23 115.9-123.0 7.1 4 MLL
    –12p11-12p13 10.2-21.8 11.6 9 CDKN1B
    –13q14 48.1-48.5 0.4 29 RFP2, BCMSUN
    –13q33-13q34 102.2-109.1 6.9 26
    +18q21 55.3-64.6 9.3 8 BCL2
    • The genomic localization information is according to the NCBI database.—indicates not applicable.

  • Table 3.

    Negative prognostic factors in MCL

    Clinical feature and genomic aberrationNo. of patientsAll patients evaluable for the characteristic % P
    Clinical feature
       LDH level elevated 10 31 32.3 < .001
       Older than 60 y 20 36 55.6 .093
       Stage III/IV 32 35 92.5 .508
       2 or more extranodal sites 24 34 70.6 .057
       WHO performance status of 2 or more 6 30 20.0 .169
    Genomic alteration
       8p21 deletion 14 36 38.9 .033
       13q14 deletion 19 36 52.8 .010