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Identification of heterologous translocation partner genes fused to the BCL6 gene in diffuse large B-cell lymphomas: 5′-RACE and LA – PCR analyses of biopsy samples

Abstract

In order to elucidate the molecular mechanism(s) for BCL6 translocation, we identified translocational partner genes by subjecting clinical biopsy samples from patients with non-Hodgkin's lymphoma to 5′-rapid amplification of cDNA ends (5′-RACE). Sequence analysis of the 5′-RACE product revealed that the BCL6 gene was fused to the J segment of the immunoglobulin heavy chain (IgH) gene in about half of the cases, but in the other half, it was fused to heterologous partners, including the MHC class II transactivator (CIITA), pim-1, eukaryotic initiation factor 4AII (eif4AII), transferrin receptor (TFRR) and ikaros genes. Since analyses using genomic long and accurate (LA) – PCR revealed that the breakpoints in the partner gene were confined to the first intron or the second exon in all cases, the promoter and the first exon of the BCL6 gene were replaced by the promoter and the first or both the first and second exon of the partner gene. The breakpoint flanking sequences had no recombination signal sequences (RSSs) or chi sequences and were homologous with the switch region only when the BCL6 gene was fused to the IgH gene, suggesting that BCL6 translocation cannot be explained solely by mistakes of V(D)J, or chi-mediated or class-switch recombination, but rather another mechanism may also be required to explain the molecular mechanism for the promiscuous BCL6 translocation.

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References

  • Akasaka T, Miura I, Takahashi N, Akasaka H, Yonetani N, Ohno H, Fukuhara S and Okuma M. . 1997 Cancer Res. 57: 7–12.

  • Baron BW, Nucifora G, McCabe N, Espinosa R, Le BM and McKeithan TW. . 1993 Proc. Natl. Acad. Sci. USA 90: 5262–5266.

  • Bastard C, Deweindt C, Kerckaert JP, Lenormand B, Rossi A, Pezzella F, Fruchart C, Duval C, Monconduit M and Tilly H. . 1994 Blood 83: 2423–2427.

  • Benardin F, Collyn d HM, Quief S, Bastard C, Leprince D and Kerckaert JP. . 1997 Oncogene 14: 849–855.

  • Chen W, lida S, Louie DC, Dalla-Favera R and Chaganti RSK. . 1998 Blood 91: 603–607.

  • Cleary ML and Sklar J. . 1985 Proc. Natl. Acad. Sci. USA 82: 7439–7443.

  • Dalla-Favera R, Bregni M, Erickson J, Patterson D, Gallo R and Croce CM. . 1982 Proc. Natl. Acad. Sci. USA 79: 7824–7827.

  • Dalla-Favera R, Martinotti S, Gallo RC, Erickson J and Croce CM. . 1983 Science 219: 963–967.

  • Dalla-Favera R. . 1993 Chromosomal Translocations Involving the c-myc Oncogene in Lymphoid Neoplasia: The Causes and Consequences of Chromosomal Aberrations. Kirsch IR. (ed.).. CRC Press: Boca Raton pp. 313–332.

    Google Scholar 

  • Dallery E., Galiegue ZS, Collyn d HM, Quief S, Denis C, Hildebrand MP, Lantoine D, Deweindt C, Tilly H, Bastard C and Kerckaert JP. . 1995 Oncogene 10: 2171–2178.

  • Gaidano G and Dalla-Favera R. . 1998 The Biology of High-Grade Malignant Lymphoma: The Lymphomas. Canellos GP, Lister TA and Sklar JLD (eds).. WB Saunders: Philadelphia pp. 353–367.

    Google Scholar 

  • Galiegue-Zouitina S, Quief S, Hildebrand M-P, Denis C, Lecocq G, Collyn-d'Hooghe M, Bastard C, Yuille M, Dyer M JS and Kerckaert JP. . 1996 Leukemia 10: 579–587.

  • Goossens T, Klein U and Kuppers R. . 1998 Proc. Natl. Acad. Sci. USA 95: 2463–2468.

  • Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, Grogan TM, Isaacson PG, Knowles DM, Mason DY, Muller-Hermelink HK, Pileri SA, Piris MA, Ralfkider E and Warnke RA. . 1994 Blood 84: 1361–1392.

  • Kerckaert JP, Deweindt C, Tilly H, Quief S, Lecocq G and Bastard C. . 1993 Nature Genet. 5: 66–70.

  • Klein U, Gossens T, Fischer M, Kanzler H, Braeuninger A, Rajewsky K and Kupper R. . 1998 Immunol. Rev. 162: 261–280.

  • Miki T, Kawamata N, Hirosawa S and Aoki N. . 1994a Blood 83: 26–32.

  • Miki T, Kawamata N, Arai A, Ohashi K, Nakamura Y, Kato A, Hirosawa A and Aoki N. . 1994b Blood 83: 217–222.

  • Motokura T, Bloom T, Kim HG, Kuppner H, Ruderman JV, Kronenberg HM and Arnold A. . 1991 Nature 350: 512–515.

  • Offit K, LoCoco F, Louie DC, Parsa NZ, Leung D, Portlock C, Ye BH, Lista F, Filippa DA, Rosenbaum A, Ladanyi M, Jhanwar S, Dalla-Favera R and Chaganti RSK. . 1994 N. Engl. J. Med. 331: 74–80.

  • Ohno H and Fukuhara S. . 1997 Leuk. Lymph. 27: 53–63.

  • Onizuka T, Moriyama M, Yamochi T, Kuroda T, Kazama A, Kanazawa N, Sato K, Kato T, Ota H and Mori S. . 1995 Blood 86: 28–37.

  • Pasqualucci L, Migliazza A, Fracchiolla N, William C, Neri A, Baldini L, Chaganti RSK, Klein U, Kuppers R, Rajewsky K and Dalla-Favera R. . 1998 Proc. Natl. Acad. Sci. USA 95: 11816–11821.

  • Shen HM, Perters A, Baron B, Zhu X and Storb U. . 1998 Science 280: 1750–1752.

  • Suzuki K, Miki T, Kawamata N, Hirosawa S, Yoshizawa K, Kiyosawa K and Aoki N. . 1994 Jpn. J. Cancer Res. 85: 911–917.

  • Taub R, Kirsch IR, Morton C, Lenoir G, Swan D, Tronick S, Aaronson S and Leder P. . 1982 Proc. Natl. Acad. Sci. USA 79: 7837–7841.

  • Tsujimoto Y, Yunis J, Onorato-Showe L, Erikson J, Nowell PC and Croce CM. . 1984 Science 224: 1403–1406.

  • Tsujimoto Y. . 1993 Human B-cell Neoplasms with the t(11;14)(q13;q32) and t(14;18)(q32;q21) Chromosome Translocations: The Causes and Consequences of Chromosomal Aberrations. Kirsch IR. (ed.).. CRC Press: Boca Raton pp. 333–350.

    Google Scholar 

  • Wyatt RT, Rudders RA, Zelenetz A, Delellis RA and Krontiris TG. . 1992 J. Exp. Med. 175: 1575–1588.

  • Ye BH, Lista F, Lo CF, Knowles DM, Offit K, Chaganti RSK and Dalla-Favera R. . 1993 Science 262: 747–750.

  • Ye BH, Chaganti RSK, Chang CC, Niu H, Corradini P, Chaganti RSK and Dalla-Favera R. . 1995 EMBO. J 14: 6209–6217.

  • Zajac-Kaye M, Gelmann EP and Levens D. . 1988 Science 240: 1776–1780.

  • Zutter MM and Korsmeyer SJ. . 1998 The Biology of Low-Grade Malignant Lymphoma: The Lymphomas. Canellos GP, Lister TA and Sklar JL. (eds).. WB Saunders: Philadelphia pp. 337–351.

    Google Scholar 

Download references

Acknowledgements

We thank Dr Tohru Miki for the gift of the ST-1 probe. We also thank Mis. Naoko Ishiguro for the assistance in preparing this manuscript.

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Yoshida, S., Kaneita, Y., Aoki, Y. et al. Identification of heterologous translocation partner genes fused to the BCL6 gene in diffuse large B-cell lymphomas: 5′-RACE and LA – PCR analyses of biopsy samples. Oncogene 18, 7994–7999 (1999). https://doi.org/10.1038/sj.onc.1203293

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