Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Leading Article
  • Published:

FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations

Abstract

The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization (FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( × 1), gastric MALT lymphoma ( × 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( × 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Kaestner KH, Knochel W, Martinez DE . Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev 2000; 14: 142–146.

    CAS  PubMed  Google Scholar 

  2. Lai E, Prezioso VR, Tao WF, Chen WS, Darnell Jr JE . Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. Genes Dev 1991; 5: 416–427.

    Article  CAS  Google Scholar 

  3. Kaufmann E, Knochel W . Five years on the wings of fork head. Mech Dev 1996; 57: 3–20.

    Article  CAS  Google Scholar 

  4. Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP . A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 2001; 413: 519–523.

    Article  CAS  Google Scholar 

  5. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001; 27: 20–21.

    Article  CAS  Google Scholar 

  6. Coffer PJ, Burgering BM . Forkhead-box transcription factors and their role in the immune system. Nat Rev Immunol 2004; 4: 889–899.

    Article  CAS  Google Scholar 

  7. Katoh M, Katoh M . Human FOX gene family (Review). Int J Oncol 2004; 25: 1495–1500.

    CAS  PubMed  Google Scholar 

  8. Borkhardt A, Repp R, Haas OA, Leis T, Harbott J, Kreuder J et al. Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23). Oncogene 1997; 14: 195–202.

    Article  CAS  Google Scholar 

  9. Hillion J, Le Coniat M, Jonveaux P, Berger R, Bernard OA . AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood 1997; 90: 3714–3719.

    CAS  PubMed  Google Scholar 

  10. Parry P, Wei Y, Evans G . Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. Genes Chromosomes Cancer 1994; 11: 79–84.

    Article  CAS  Google Scholar 

  11. Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher III FJ, Emanuel BS et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet 1993; 5: 230–235.

    Article  CAS  Google Scholar 

  12. Davis RJ, D'Cruz CM, Lovell MA, Biegel JA, Barr FG . Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. Cancer Res 1994; 54: 2869–2872.

    CAS  PubMed  Google Scholar 

  13. Lin L, Miller CT, Contreras JI, Prescott MS, Dagenais SL, Wu R et al. The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas. Cancer Res 2002; 62: 5273–5279.

    CAS  PubMed  Google Scholar 

  14. Banham AH, Beasley N, Campo E, Fernandez PL, Fidler C, Gatter K et al. The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. Cancer Res 2001; 61: 8820–8829.

    CAS  PubMed  Google Scholar 

  15. Kok K, Naylor SL, Buys CH . Deletions of the short arm of chromosome 3 in solid tumors and the search for suppressor genes. Adv Cancer Res 1997; 71: 27–92.

    Article  CAS  Google Scholar 

  16. Shaffer AL, Rosenwald A, Staudt LM . Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol 2002; 2: 920–932.

    Article  CAS  Google Scholar 

  17. Barrans SL, Fenton JA, Banham A, Owen RG, Jack AS . Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood 2004; 104: 2933–2935.

    Article  CAS  Google Scholar 

  18. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103: 275–282.

    Article  CAS  Google Scholar 

  19. Banham AH, Connors JM, Brown PJ, Cordell JL, Ott G, Sreenivasan G et al. Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin Cancer Res 2005; 11: 1065–1072.

    CAS  PubMed  Google Scholar 

  20. Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK et al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21)p6 associated with mucosa-associated lymphoid tissue lymphomas. Blood 1999; 93: 3601–3609.

    CAS  Google Scholar 

  21. Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott G et al. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 2003; 101: 2335–2339.

    Article  CAS  Google Scholar 

  22. Mitelman Database of Chromosome Aberrations in Cancer (2003), Mitelman F, Johansson B, Mertens F (eds).http://cgap.nci/nih.gov/Chromosomes/MItelman.2004.

  23. Dierlamm J, Wlodarska I, Michaux L, Stefanova M, Hinz K, Van den BH et al. Genetic abnormalities in marginal zone B-cell lymphoma. Hematol Oncol 2000; 18: 1–13.

    Article  CAS  Google Scholar 

  24. Thome M . CARMA1, BCL-10 and MALT1 in lymphocyte development and activation. Nat Rev Immunol 2004; 4: 348–359.

    Article  CAS  Google Scholar 

  25. Isaacson PG, Du MQ . MALT lymphoma: from morphology to molecules. Nat Rev Cancer 2004; 4: 644–653.

    Article  CAS  Google Scholar 

  26. Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A . T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia 2005; 19: 652–658.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank AH Banham (John Radcliffe Hospital, University of Oxford, Oxford, UK) for providing the JC12 antibody, U Pluys and S Karanfil for technical assistance in FISH and IHC analysis, respectively, R Schots (AZ-VUB Jette, Brussels) and V Madoe (St Salvatorziekenhuis, Hasselt) for clinical data and R Logist for clerical help.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to I Wlodarska.

Additional information

This text presents research results of the Belgian program of Interuniversity Poles of attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The scientific responsibility is assumed by the authors. P Vandenberghe is a Clinical Investigator of FWO-Vlaanderen

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wlodarska, I., Veyt, E., De Paepe, P. et al. FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations. Leukemia 19, 1299–1305 (2005). https://doi.org/10.1038/sj.leu.2403813

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403813

Keywords

This article is cited by

Search

Quick links