A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in a diffuse large B-cell lymphoma

Wang, Huan-You; Bossler, Aaron; Schaffer, András; Tomczak, Ewa; DiPatri, Doris; Frank, Dale; Nowell̀, Peter C.; Bagg, Adam

doi:10.1016/j.cancergencyto.2006.07.016

Cited by 18 publications

(11 citation statements)

References 32 publications

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“…In four cases, we observed involvement of the MYC and BCL6 genes within one translocation corresponding to previous reports on the rare occurrence of this type of alteration in mature B-cell neoplasms (Wang et al, 2007). Nine of the 10 cases from this study were classified as aggressive lymphoma entities (in most cases BL/mature B-ALL), but one triple hit lymphoma case was represented by FL.…”

Section: Discussionsupporting

confidence: 71%

Several lymphoma‐specific genetic events in parallel can be found in mature B‐cell neoplasms

Bacher

Haferlach

Alpermann

et al. 2010

Genes Chromosomes & Cancer

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The mature B-cell neoplasms frequently result from translocations involving the IGH gene localized on 14q32. In rare instances, combinations of different IGH rearrangements were described, and even coincidence of three genetic lymphoma-specific events has been rarely reported. We here present eight patients with triple hit lymphoma, and two with four different lymphoma specific events detected by chromosome banding analysis and interphase FISH (seven males, three females, 47-82 years). All showed bone marrow involvement (Burkitt's lymphoma: n = 5, diffuse large B-cell lymphoma: n = 2; features intermediate between BL/DLBCL: n = 1; secondary aggressive B-cell lymphoma: n = 1; follicular lymphoma: n = 1). Eight patients had triple hit lymphoma combining IGH-BCL2/t(14;18)(q32;q21), MYC/8q24, and BCL6/3q27 rearrangements. Two showed an additional IGH-CCND1/t(11;14)(q13;q32) as fourth genetic event (according to research of the Mitelman database, the first reports on four genetic hits in lymphomas). All cases had complex aberrant karyotypes (median, 11 cytogenetic alterations per patient). Interphase FISH revealed a high rate of CDKN2A deletions (five of nine cases investigated; 56%), being homozygous in two of these cases. At the time of study, four of nine patients with follow-up data were alive (44%), one of these in remission. The two patients with four genetic hits died 6 and 9 days from diagnosis. Additional cases of lymphomas with three or four genetic hits should be collected to evaluate whether their clinical course differs from dual hit lymphomas.

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Section: Discussionsupporting

confidence: 71%

Several lymphoma‐specific genetic events in parallel can be found in mature B‐cell neoplasms

Bacher

Haferlach

Alpermann

et al. 2010

Genes Chromosomes & Cancer

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“…[30][31][32] In four cases (11%), MYC rearrangements were detectable only with the dual-fusion probe (Figure 1b) and thus corresponded to t(8;14) with MYC breaks 4100-bp 5 0 to the first gene exon, which are typical for endemic Burkitt lymphomas and are not detectable by the applied break-apart probe. 33,34 Three cases with MYC breaks showed telomeric deletions and one telomeric amplification or double minutes.…”

Section: Fluorescence In Situ Hybridizationmentioning

confidence: 99%

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

et al. 2014

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In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using break-apart probes and IGH/MYC dual-fusion probes. Concurrent BCL2 and BCL6 aberrations were also assessed. Data were correlated with clinicopathological variables and prognostic parameters. MYC rearrangements were observed in 39/432 evaluable cases (9%), including 4 rearrangements detectable only with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P ¼ 0.02), MYC protein expression (P ¼ 0.032), and larger tumor mass size (P ¼ 0.0003). Patients with MYC rearrangements were more likely to be treatment resistant (Po0.0001). All types of MYC rearrangements were associated with poorer disease-specific survival, that is, 20/39 dead, median disease-specific survival 42 months, compared with 98/393 dead among the nonrearranged cases, median disease-specific survival not reached (P ¼ 0.0002). Cases with MYC rearrangements that overexpressed MYC protein were at risk with respect to disease-specific survival independent of the International Prognostic Index (P ¼ 0.046 and Po0.001, respectively). Presence of concurrent BCL2 aberrations but not of BCL6 aberrations was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC

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“…BCL2 on 18q21 is the most common partner, but several other partner chromosome loci have been reported. Moreover, C-MYC has been found to undergo translocation with diverse nonimmunoglobulin gene (IG) loci, such as 2p15, 3q27, 7p12, and 9p13 in various B-cell malignancies [26][27][28][29][30][31]. In addition to B-cell lymphoid tumors, myeloma cell lines show highly complex C-MYC translocations [32,33].…”

Section: Discussionmentioning

confidence: 99%

Establishment of CD5 and CD10 double-positive mature B-cell line, WILL1, showing complex 8q24 translocation involving 14q32 and 6q27

et al. 2008

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We established a novel mature B-cell line from a CD5 and CD10 double-positive diffuse large B-cell lymphoma patient, designated as WILL1. WILL1 cells were positive for CD5, CD10, CD19, and CD20. Spectral karyotype (SKY) analysis revealed chromosome 8 signals on 6q27 as well as 14q32. Fluorescence in situ hybridization (FISH) analysis suggested that a translocation break occurred outside the immunoglobulin heavy chain (IGH) gene on 14q32. Moreover, fusion signals of IGH and C-MYC probes were detected on the derivative 6 and derivative 14 chromosomes. Southern blot analysis using a C-MYC exon II fragment failed to detect rearrangement, suggesting that the 8q24 breakpoints lay far up- or downstream of the C-MYC gene. WILL1 is a useful tool to analyze the pathogenesis of CD5 and CD10 double-positive diffuse large B-cell lymphoma, and for molecular cloning of the unique translocation breakpoints of 14q32 and 8q24 and a novel gene on 6q27.

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A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in a diffuse large B-cell lymphoma

Cited by 18 publications

References 32 publications

Several lymphoma‐specific genetic events in parallel can be found in mature B‐cell neoplasms

Several lymphoma‐specific genetic events in parallel can be found in mature B‐cell neoplasms

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

Establishment of CD5 and CD10 double-positive mature B-cell line, WILL1, showing complex 8q24 translocation involving 14q32 and 6q27

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