-
Shahrzad Negahban,
Nasrollah Ahmadi,
Ahmad Oryan,
Habib N. Khojasteh,
Azita Aledavood,
Hossein Soleimanpour,
Mohammad Mohammadianpanah,
Ilske Oschlies, Stefan Gesk,
Reiner Siebert,
Khosrow Daneshbod,
Yahya Daneshbod
-
Claudia Otto,
Maciej Giefing,
Anne Massow,
Inga Vater, Stefan Gesk,
Matthias Schlesner,
Julia Richter,
Wolfram Klapper,
Martin-Leo Hansmann,
Reiner Siebert,
Ralf Küppers
[show abstract]
[hide abstract]
ABSTRACT: Hodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) show constitutive activation of nuclear factor (NF)-κB. Several genetic lesions contribute to this deregulated NF-κB activity. Here, we analysed two further NF-κB regulators for genetic lesions, the inhibitory factor TRAF3 and the key signalling component of the alternative NF-κB pathway, MAP3K14 (NIK). Single nucleotide polymorphism (SNP) array analysis of cHL cell lines revealed a uniparental disomy of the long arm of chromosome 14 associated with a biallelic deletion of TRAF3 located on this chromosome in cell line U-HO1. Cloning of the deletion breakpoint showed a 123 371 bp deletion. No inactivating mutations of TRAF3 were found in six other cHL cell lines or in microdissected HRS cells from seven cHL. However, in primary cHL samples interphase cytogenetic analyses revealed signal patterns indicating monoallelic deletion of TRAF3 in 3/20 other cases. SNP array analysis revealed a gain of copy number for MAP3K14 in three cHL cell lines. Gains of MAP3K14 were detected in 5/16 cases of primary cHL. In conclusion, in rare instances, HRS cells harbour inactivating mutations of the TRAF3 gene and recurrently show gains of MAP3K14, indicating that more components of NF-κB signalling show genetic lesions in HRS cells than previously known.
British Journal of Haematology 04/2012; 157(6):702-8. · 4.94 Impact Factor
-
Itziar Salaverria,
Takashi Akasaka, Stefan Gesk,
Monika Szczepanowski,
Birgit Burkhardt,
Lana Harder,
Christine Damm-Welk,
Ilske Oschlies,
Wolfram Klapper,
Martin J S Dyer,
Reiner Siebert
[show abstract]
[hide abstract]
ABSTRACT: Translocations involving immunoglobulin (IG) loci are the hallmarks of several subtypes of B-cell lymphoma. Common to these translocations is that cellular proto-oncogenes come under the influence of IG regulatory elements leading to deregulated expression. In case of a breakpoint in the IGH switch region, oncogene activation can take place on both derivative chromosomes, which means that in principle one translocation can result in concurrent activation of two genes. By fluorescence in situ hybridization (FISH), we identified a case of leukemic B-cell lymphoma in a child with an IGH break and unknown partner. Subsequent long-distance inverse PCR revealed fusion of IGH Sl in 14q32 and the 50 region of CBFA2T3 in 16q24.3, suggesting presence of the t(14;16)(q32;q24.3). Candidate oncogenes targeted through this translocation are CBFA2T3 and ACSF3, which could be activated on der(16) and der(14), respectively. FISH screening of a population-based cohort of B-cell lymphomas from a prospective trial for the treatment of lymphoma in childhood (BFM-NHL) identified additionally a follicular lymphoma Grade 3/diffuse large B-cell lymphoma with IGH-CBFA2T3/ACSF3 juxtaposition. Both lymphomas shared expression of CD10 and CD20 in the absence of TdT, suggesting a germinal center (GC) B-cell origin. Our data indicate that the CBFA2T3/ACSF3 locus is a novel recurrent oncogenic target of IGH translocations, which might contribute to the pathogenesis of pediatric GC-derived B-cell lymphoma.
Genes Chromosomes and Cancer 04/2012; 51(4):338-43. · 3.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chromosomal abnormalities, like deletions, amplifications, inversions or translocations, are recurrent features in haematological malignancies. However, the precise molecular breakpoints are frequently not determined. Here we describe a rapid analysis of genetic imbalances combining fine tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR). We clarified an inv(14)(q11q32) in a case of T cell acute lymphoblastic leukaemia with a breakpoint in the TRA/D in 68% of cells detected by fluorescence in situ hybridization. FT-CGH showed several mono- and biallelic losses within TRA/D. LM-PCR disclosed a TRA/D rearrangement on one allele. The other allele revealed an inv(14)(q11q32), joining TRDD2 at 21,977,000 of 14q11 together with the IGH locus at 105,948,000 and 3'-sequence of TRAC at 22,092,000 joined together with IGHV4-61 at 106,166,000. This sensitive approach can unravel complex chromosomal abnormalities in patient samples with a limited amount of aberrant cells and may lead to better diagnostic and therapeutic options.
Acta Haematologica 01/2012; 127(1):16-9. · 1.35 Impact Factor
-
Chris Pepper,
Aneela Majid,
Thet Thet Lin,
Saman Hewamana,
Guy Pratt,
Renata Walewska, Stefan Gesk,
Reiner Siebert,
Simon Wagner,
Ben Kennedy,
Fiona Miall,
Zadie A Davis,
Ian Tracy,
Anne C Gardiner,
Paul Brennan,
Robert K Hills,
Martin J S Dyer,
David Oscier,
Chris Fegan
[show abstract]
[hide abstract]
ABSTRACT: Approximately 70% of chronic lymphocytic leukaemia (CLL) patients present with early stage disease, therefore defining which patients will progress and require treatment is a major clinical challenge. Here, we present the largest study of prognostic markers ever carried out in Binet stage A patients (n = 1154) with a median follow-up of 8 years. We assessed the prognostic impact of lymphocyte doubling time (LDT), immunoglobulin gene (IGHV) mutation status, CD38 expression, ZAP-70 expression and fluorescence in situ hybridization (FISH) cytogenetics with regards to time to first treatment (TTFT) and overall survival (OS). Univariate analysis revealed LDT as the most prognostic parameter for TTFT, with IGHV mutation status most prognostic for OS. CD38 expression, ZAP-70 expression and FISH were also prognostic variables; combinations of these markers increased prognostic power in concordant cases. Multivariate analysis revealed that only LDT, IGHV mutation status, CD38 and age at diagnosis were independent prognostic variables for TTFT and OS. Therefore, IGHV mutation status and CD38 expression have independent prognostic value in early stage CLL and should be performed as part of the routine diagnostic workup. ZAP-70 expression and FISH were not independent prognostic markers in early stage disease and can be omitted at diagnosis but FISH analysis should be undertaken at disease progression to direct treatment strategy.
British Journal of Haematology 12/2011; 156(4):499-507. · 4.94 Impact Factor
-
Elena Beltran,
Vicente Fresquet,
Javier Martinez-Useros,
Jose A Richter-Larrea,
Ainara Sagardoy,
Izaskun Sesma,
Luciana L Almada,
Santiago Montes-Moreno,
Reiner Siebert, Stefan Gesk,
Maria J Calasanz,
Raquel Malumbres,
Melissa Rieger,
Felipe Prosper,
Izidore S Lossos,
Miguel Angel Piris,
Martin E Fernandez-Zapico,
Jose A Martinez-Climent
[show abstract]
[hide abstract]
ABSTRACT: The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 overexpression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current treatment strategies. Cyclin-D1 has been postulated as an effective therapeutic target, but the evaluation of this target has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model in which cyclin-D1 expression can be regulated externally. These mice developed cyclin-D1-expressing lymphomas capable of recapitulating features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo; however, using a combination of in vitro and in vivo assays, we identified a novel prosurvival cyclin-D1 function in MCL cells. Specifically, we found that cyclin-D1, besides increasing cell proliferation through deregulation of the cell cycle at the G(1)-S transition, sequestrates the proapoptotic protein BAX in the cytoplasm, thereby favoring BCL2's antiapoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a proapoptotic BH3 mimetic synergistically killed the cyclin-D1-expressing murine lymphomas, human MCL cell lines, and primary lymphoma cells. Our study identifies a role of cyclin-D1 in deregulating apoptosis in MCL cells, and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. This effective combination therapy also might be exploited in other cyclin-D1-expressing tumors.
Proceedings of the National Academy of Sciences 07/2011; 108(30):12461-6. · 9.68 Impact Factor
-
Martin Hasselblatt, Stefan Gesk,
Florian Oyen,
Sabrina Rossi,
Elisabetta Viscardi,
Felice Giangaspero,
Caterina Giannini,
Alexander R Judkins,
Michael C Frühwald,
Tobias Obser,
Reinhard Schneppenheim,
Reiner Siebert,
Werner Paulus
[show abstract]
[hide abstract]
ABSTRACT: Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive brain tumors of early childhood poorly responding to therapy. The majority of cases show inactivation of SMARCB1 (INI1, hSNF5, BAF47), a core member of the adenosine triphosphate (ATP)-dependent SWI/SNF chromatin-remodeling complex. We here report the case of a supratentorial AT/RT in a 9-month-old boy, which showed retained SMARCB1 staining on immunohistochemistry and lacked genetic alterations of SMARCB1. Instead, the tumor showed loss of protein expression of another SWI/SNF chromatin-remodeling complex member, the ATPase subunit SMARCA4 (BRG1) due to a homozygous SMARCA4 mutation [c.2032C>T (p.Q678X)]. Our findings highlight the role of SMARCA4 in the pathogenesis of SMARCB1-positive AT/RT and the usefulness of antibodies directed against SMARCA4 in this diagnostic setting.
The American journal of surgical pathology 06/2011; 35(6):933-5. · 4.06 Impact Factor
-
Itziar Salaverria,
Claudia Philipp,
Ilske Oschlies,
Christian W Kohler,
Markus Kreuz,
Monika Szczepanowski,
Birgit Burkhardt,
Heiko Trautmann, Stefan Gesk,
Miroslaw Andrusiewicz, [......],
Julia Richter,
Maciej Rosolowski,
Carsten Schwaenen,
Harald Stein,
Lorenz Trümper,
Swen Wessendorf,
Rainer Spang,
Ralf Küppers,
Wolfram Klapper,
Reiner Siebert
[show abstract]
[hide abstract]
ABSTRACT: The prognosis of germinal center-derived B-cell (GCB) lymphomas, including follicular lymphoma and diffuse large-B-cell lymphoma (DLBCL), strongly depends on age. Children have a more favorable outcome than adults. It is not known whether this is because of differences in host characteristics, treatment protocols, or tumor biology, including the presence of chromosomal alterations. By screening for novel IGH translocation partners in pediatric and adult lymphomas, we identified chromosomal translocations juxtaposing the IRF4 oncogene next to one of the immunoglobulin (IG) loci as a novel recurrent aberration in mature B-cell lymphoma. FISH revealed 20 of 427 lymphomas to carry an IG/IRF4-fusion. Those were predominantly GCB-type DLBCL or follicular lymphoma grade 3, shared strong expression of IRF4/MUM1 and BCL6, and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas differed from other subtypes of DLBCL. A classifier for IG/IRF4 positivity containing 27 genes allowed accurate prediction. IG/IRF4 positivity was associated with young age and a favorable outcome. Our results suggest IRF4 translocations to be primary alterations in a molecularly defined subset of GCB-derived lymphomas. The probability for this subtype of lymphoma significantly decreases with age, suggesting that diversity in tumor biology might contribute to the age-dependent differences in prognosis of lymphoma.
Blood 04/2011; 118(1):139-47. · 9.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report on a prenatally diagnosed de novo small supernumerary marker chromosome (sSMC) derived form chromosome 18. Molecular cytogenetic studies led to information about the clinical relevance of the sSMC-induced chromosomal imbalance. As prenatal ultrasound was normal, detailed information with respect to prenatal counseling of the parents was necessary. In general, detection of an sSMC requires as much information on the exact genetic content with its possible impact on the phenotype as achievable.
Amniocentesis was performed in a 37-year-old Gravida IV Para II with a history of an induced abortion due to a prenatally diagnosed trisomy 21. Fluorescence in situ hybridization quick test gave hint on a possible mosaic trisomy 18, whereas the conventional banding cytogenetic analysis revealed an sSMC. The amount of euchromatin was estimated to be less than 5 MB.
sSMC are rare, being present in less than 0.08% of all pregnancies. Going together with an abnormal ultrasound, counseling of the parents is relatively easy to perform. In cases of normal prenatal ultrasound, profound knowledge about the surplus genetic content is necessary for the estimation of the fetal outcome prognosis. In the present case, detailed molecular cytogenetics techniques led the parents to continue the pregnancy.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 04/2011; 25(2):200-2. · 1.36 Impact Factor
-
British Journal of Haematology 02/2011; 153(4):533-5. · 4.94 Impact Factor
-
Ludger Sellmann,
Rene Scholtysik,
Markus Kreuz,
Sandra Cyrull,
Enrico Tiacci,
Jens Stanelle,
Alexander Carpinteiro,
Holger Nückel,
Tanja Boes, Stefan Gesk,
Reiner Siebert,
Ludger Klein-Hitpass,
Ulrich Dührsen,
Jan Dürig,
Ralf Küppers
[show abstract]
[hide abstract]
ABSTRACT: To understand the influence of chromosomal alterations on gene expression in a genome-wide view, chromosomal imbalances detected by single nucleotide polymorphism (SNP) chips were compared with global gene expression in 16 cases of chronic lymphocytic leukemia (CLL). A strong concordance between chromosomal gain or loss and increased or reduced expression of genes in the affected regions was found, respectively. Regions of uniparental disomy (UPD) were rare and had usually no consistent influence on gene expression, but in one instance, a large UPD was associated with a downregulation of most genes in the affected chromosome. The frequently deleted miRNAs, MIRN15A and MIRN16-1, did not show a reduced expression in cases with monoallelic deletions. The BCL2 protein, considered to be downregulated by these miRNAs, was upregulated not only in CLL with biallelic deletion of MIRN15A and MIRN16-1, but also in cases with monoallelic deletion. This suggests a complex regulation of BCL2 levels in CLL cells. Taken together, in CLL, a global gene dosage effect exists for chromosomal gains and deletions and in some instances for UPDs. We did not confirm a consistent correlation between MIRN15A and MIRN16-1 expression levels and BCL2 protein levels, indicating a complex regulation of BCL2 expression.
Cancer genetics and cytogenetics 12/2010; 203(2):149-60. · 1.54 Impact Factor
-
Leukemia research 12/2010; 35(5):e55-7. · 2.36 Impact Factor
-
Shahrzad Negahban,
Inga Nagel,
Hossein Soleimanpour,
Azita Aledavood,
Neda Bagheri,
Mehdi Paydar,
Khosrow Daneshbod,
Martin Hasselblatt, Stefan Gesk,
Reiner Siebert,
Yahya Daneshbod
Journal of Clinical Oncology 11/2010; 28(33):e688-91. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chromosomal aberrations have diagnostic, prognostic, and therapeutic relevance in hematologic malignancies. By combining fine-tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR), we established a fast, robust approach to precisely characterize chromosomal breakpoints. Using this approach, we clarified at the molecular level novel chromosomal translocation t(12;14)(q23;q11.2) in T-lymphoblastic lymphoma. The translocation occurred during the deletional rearrangement of the T-cell receptor delta gene (TRD), which is a pivotal step in T cell differentiation toward the alpha/beta vs. the gamma/delta lineage. We found that this rearrangement disrupted the hypothetical gene C12orf42 and brought the Achaete-scute complex homolog 1 gene into proximity of the TRA enhancer, which encodes a member of the basic helix-loop-helix family of transcription factors and is overexpressed in thyroid and lung cancers.
European Journal Of Haematology 11/2010; 85(5):452-6. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Typical Williams-Beuren syndrome (WBS) is commonly caused by a ~1.5 Mb - ~1.8 Mb heterozygous deletion of contiguous genes at chromosome region 7q11.23. The majority of WBS cases occurs sporadically but few familial cases of autosomal dominant inheritance have been reported. Recent data demonstrated the existence of the paracentric inversion polymorphism at the WBS critical region in 7q11.23 in some of the progenitors transmitting the chromosome which shows the deletion in the affected child. In parents having a child affected by WBS the prevalence of such a structural variant has been reported to be much higher (~25- ~30%) than in the general population (~1- ~6%). However, in these previously reported studies only a limited number of randomly selected patients and non transmitting parents of WBS patients were used as controls, but without specification of any clinical data. Therefore we have undertaken a German population-based molecular cytogenetic investigation. We evaluated the incidence of the paracentric inversion polymorphism at 7q11.23 analyzing interphase nuclei of lymphocytes using a three color fluorescence in situ hybridization (FISH) probe.
FISH analysis was carried out on couples with a child affected by WBS as compared to a population sample composed of different normal individuals: Control group I: couples with two healthy children, control group II: couples with fertility problems, planning ICSI and control group III: couples with two healthy children and one child with a chromosome aberration, not involving region 7q11.23. The three color FISH assay showed that the frequency of the paracentric inversion polymorphism at 7q11.23 in couples with a child affected by WBS was 20.8% (5 out of 24 pairs) as compared to 8.3% (2 out of 24 pairs, control group I), 25% (4 out of 16 pairs, control group II) and 9.1% (1 out of 11 pairs, control group III), respectively (total 7 out of 51 pairs, 13.8%). The frequencies differed between the groups, but this was statistically not significant (p > 0.05, Fisher's test).
Our results do not support the hypothesis that the paracentric inversion polymorphism at 7q11.23 is a major predisposing factor for the WBS deletion.
Molecular Cytogenetics 11/2010; 3:21.
-
[show abstract]
[hide abstract]
ABSTRACT: Primary CNS lymphoma (PCNSL), the intracerebral subgroup of diffuse large B cell lymphoma (DLBCL), shows evidence for aberrant activation of the nuclear factor (NF)-kappaB pathway. In order to identify potential activators of the NF-kappaB complex, we analyzed the CARD11 and TNFAIP3 genes for the presence of somatic mutations and TNFAIP3 for aberrant promoter methylation in PCNSL. We also compared PCNSL to spinal DLBCL, because CARD11 and TNFAIP3 mutations have been described in systemic DLBCL. CARD11 mutations, located in the coiled-coil region, which may activate NF-kappaB, were detected in 16% (5/32) of PCNSL, while TNFAIP3 mutations were detected in 3% (1/32) of PCNSL. In PCNSL, all CARD11 mutations were heterozygous, in-frame, induced amino acid exchanges, and presumably led to activation of this oncogene. Spinal DLBCL harbored mutations of CARD11 and TNFAIP3 in 10% (1/10) and 20% (2/10) of cases, respectively. In both PCNSL and spinal DLBCL, mutations in CARD11 and TNFAIP3 were mutually exclusive. TNFAIP3 was unmethylated in all PCNSLs (30/30) and spinal DLBCLs (10/10). We conclude that mutations of the oncogene CARD11 may contribute to NF-kappaB activation and thereby play a role in the pathogenesis of PCNSL, while, in contrast to systemic DLBCL, inactivation of TNFAIP3 either by mutation or methylation seems to be of minor significance.
Acta Neuropathologica 10/2010; 120(4):529-35. · 9.32 Impact Factor
-
Marta Salido,
Cristina Baró,
David Oscier,
Kostas Stamatopoulos,
Judith Dierlamm,
Estela Matutes,
Alexandra Traverse-Glehen,
Francoise Berger,
Pascale Felman,
Catherine Thieblemont, [......],
Blanca Espinet,
Elisa Luño,
Iwona Wlodarska,
Gregor Verhoef,
Marta García-Granero,
Antonio Salar,
Theodora Papadaki,
Sergio Serrano,
Miguel A Piris,
Francesc Solé
[show abstract]
[hide abstract]
ABSTRACT: We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.
Blood 09/2010; 116(9):1479-88. · 9.90 Impact Factor
-
Annette Schmidt,
Roland Schmitz,
Maciej Giefing,
Jose Ignacio Martin-Subero, Stefan Gesk,
Inga Vater,
Anne Massow,
Ewerton Maggio,
Markus Schneider,
Martin-Leo Hansmann,
Reiner Siebert,
Ralf Küppers
[show abstract]
[hide abstract]
ABSTRACT: Survival of the malignant Hodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is dependent on constitutive activation of the nuclear factor kappaB (NF-kappaB) transcription factor. The deubiquitinating enzyme CYLD is a negative regulator of NF-kappaB and known to function as a tumor suppressor. To determine whether CYLD mutations play a role in cHL pathogenesis, we sequenced the gene in cHL cell lines and microdissected HRS cells obtained from lymph-node biopsies. A biallelic inactivation by mutations was found in the cHL cell-line KM-H2. However, the other seven cHL cell lines analyzed and HRS cells of 10 primary cHL cases did not show any mutations. By interphase cytogenetics, a (sub)clonal biallelic CYLD deletion was observed by interphase cytogenetics in 1 of 29 primary cHL, whereas signal patterns indicating decreased CYLD copy numbers were observed in a total of 10 of 29 primary cases. Our results suggest that biallelic CYLD mutations are rarely involved in cHL pathogenesis. Nevertheless, it is remarkable that KM-H2 cells, besides the CYLD mutations, also carry inactivating mutations in the genes of two other NF-kappaB inhibitors, that is, NFKBIA and TNFAIP3, exemplifying that multiple lesions in regulators of this signaling pathway can likely cooperatively contribute to the strong NF-kappaB activity of these cells.
Genes Chromosomes and Cancer 09/2010; 49(9):803-9. · 3.31 Impact Factor
-
Shahrzad Negahban,
Nasrollah Ahmadi,
Ahmad Oryan,
Habib N Khojasteh,
Azita Aledavood,
Hossein Soleimanpour,
Mohammad Mohammadianpanah,
Ilske Oschlies, Stefan Gesk,
Reiner Siebert,
Khosrow Daneshbod,
Yahya Daneshbod
[show abstract]
[hide abstract]
ABSTRACT: Burkitt lymphoma (BL) is a highly aggressive neoplasm, which frequently affects the ileocecal region in the sporadic form and the jaw in the endemic form; however, the breast is a rare primary site of this tumor. Here we describe a case of primary bilateral breast BL presenting during lactation in a 23-year-old woman. Excisional biopsy of breast masses demonstrated a B-cell lymphoma with a characteristic 'starry sky' pattern highly suggestive of BL. The neoplastic cells strongly expressed CD20 and CD10, and showed proliferative activity as measured by Ki-67. An IGH-MYC gene fusion indicating the presence of a typical Burkitt translocation t(8;14)(q24;q32) in the tumor tissue was detected by fluorescent in situ hybridization. The present case, along with a comprehensive review of the literature, demonstrates that BL of the breast should be considered in the differential diagnosis of lesions of the breast during lactation. Whether hormonal or antigenic factors trigger Burkitt lymphomagenesis in the lactating breast warrants further investigation.
Molecular diagnosis & therapy 08/2010; 14(4):243-50. · 1.71 Impact Factor
-
Inga Nagel,
Monika Szczepanowski,
José I Martín-Subero,
Lana Harder,
Takashi Akasaka,
Ole Ammerpohl,
Evelyne Callet-Bauchu,
Randy D Gascoyne, Stefan Gesk,
Doug Horsman,
Wolfram Klapper,
Aneela Majid,
José A Martinez-Climent,
Stephan Stilgenbauer,
Holger Tönnies,
Martin J S Dyer,
Reiner Siebert
[show abstract]
[hide abstract]
ABSTRACT: Sequence variants at the TERT-CLPTM1L locus in chromosome 5p have been recently associated with disposition for various cancers. Here we show that this locus including the gene encoding the telomerase reverse-transcriptase TERT at 5p13.33 is rarely but recurrently targeted by somatic chromosomal translocations to IGH and non-IG loci in B-cell neoplasms, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. In addition, cases with genomic amplification of TERT locus were identified. Tumors bearing chromosomal aberrations involving TERT showed higher TERT transcriptional expression and increased telomerase activity. These data suggest that deregulation of TERT gene by chromosomal abnormalities leading to increased telomerase activity might contribute to B-cell lymphomagenesis.
Blood 05/2010; 116(8):1317-20. · 9.90 Impact Factor
