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BCL2 and BCL6 atypical/unbalanced gene rearrangements in diffuse large B-cell lymphoma are indicators of an aggressive clinical course
  1. Alicia Tourneret1,2,
  2. Melissa Alame1,3,
  3. Valerie Rigau1,2,
  4. Luc Bauchet1,4,
  5. Michel Fabbro5,
  6. Laura De Oliveira2,
  7. Valere Cacheux1,3,
  8. Valerie Costes1,2,
  9. Vanessa Lacheretz-Szablewski1,2
  1. 1Université de Montpellier, Montpellier, France
  2. 2Département de Pathologie, CHU Montpellier, Montpellier, France
  3. 3Département d'Hematologie Biologique, CHU Montpellier, Montpellier, France
  4. 4Département de Neurochirurgie, CHU Montpellier, Montpellier, France
  5. 5ICM Montpellier, Montpellier, France
  1. Correspondence to Dr Vanessa Lacheretz-Szablewski, CHU Montpellier, Montpellier 34295, France; vszmed{at}hotmail.fr

Abstract

Aims Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin's lymphoma that represents a heterogeneous group of disease that is differentially characterised by clinical, molecular and cytogenetic features. MYC, BCL2 and BCL6 gene rearrangements have been identified as prognostic factors in DLBCL, especially for MYC. Nevertheless the frequency and effect of atypical/unbalanced BCL6, BCL2 and MYC translocations in DLBCL is not fully documented. Here, we aimed to analyse those atypical/unbalanced rearrangements in DLBCL and to assess their prognostic impact.

Methods We collected tumour tissue and clinical data from 97 DLBCL and used interphase fluorescence in situ hybridisation (FISH) with break-apart probe to characterise BCL6, BCL2 and MYC gene pattern.

Results 19 of 97 (19,6%) cases of DLBCL had atypical/ unbalanced gene rearrangements (14 involving BCL6 gene, 5 involving BCL2 gene and none involving MYC gene). Compared with patients with simple gene rearrangement and patients without cytogenetic abnormality, patients with atypical/unbalanced gene rearrangement were in an unfavourable risk group by the International Prognostic Index (p=0039), died of disease (p=0012), harboured relapse or progression (p=0011) and had shorter overall (p=0,04), relapse free (p=0029) and event free (p=0026) survival.

Conclusions We showed that patients with DLBCL with BCL2 or BCL6 atypical/unbalanced rearrangements constituted a group of patients with poor outcome. We also underlined the importance of FISH analyses, easily feasible in routine practise, at diagnosis of DLBCL to detect the rather frequent and clinically significant atypical/unbalanced aberrations of these genes.

  • lymphoma
  • cytogenetics
  • pathology
  • molecular
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Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributors VL-S, MA, VCa, VR and VCo designed the research project. VL-S, AT, VR and VCa evaluated the histological and immunohistochemical findings. VL-S, MA, LDO, AT and VCa evaluated the cytogenetic findings. VL-S and AT and MA obtained data and wrote the main part of the manuscript. VCa, MA, LB, MF, LDO, AT, VR and VCo reviewed the draft with critical comments.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the research ethics boards of our institution (Centre des Ressources Biologiques, Montpellier) according to the Declaration of Helsinki. Written consent was obtained from patients.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available.

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