Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1992 Jun 1; 175(6): 1575–1588.
PMCID: PMC2119260

BCL2 oncogene translocation is mediated by a chi-like consensus


Examination of 64 translocations involving the major breakpoint region (mbr) of the BCL2 oncogene and the immunoglobulin heavy chain locus identified three short (14, 16, and 18 bp) segments within the mbr at which translocations occurred with very high frequency. Each of these clusters was associated with a 15-bp region of sequence homology, the principal one containing an octamer related to chi, the procaryotic activator of recombination. The presence of short deletions and N nucleotide additions at the breakpoints, as well as involvement of JH and DH coding regions, suggested that these sequences served as signals capable of interacting with the VDJ recombinase complex, even though no homology with the traditional heptamer/spacer/nonamer (IgRSS) existed. Furthermore, the BCL2 signal sequences were employed in a bidirectional fashion and could mediate recombination of one mbr region with another. Segments homologous to the BCL2 signal sequences flanked individual members of the XP family of diversity gene segments, which were themselves highly overrepresented in the reciprocal products (18q-) of BCL2 translocation. We propose that the chi-like signal sequences of BCL2 represent a distinct class of recognition sites for the recombinase complex, responsible for initiating interactions between regions of DNA separated by great distances, and that BCL2 translocation begins by a recombination event between mbr and DXP chi signals. Since recombinant joints containing chi, not IgRSS, occur in brain cells expressing RAG-1 (Matsuoka, M., F. Nagawa, K. Okazaki, L. Kingsbury, K. Yoshida, U. Muller, D. T. Larue, J. A. Winer, and H. Sakano. 1991. Science [Wash. DC]. 254:81; reference 1), we further suggest that the product of this gene could mediate both BCL2 translocation and the first step of normal DJ assembly through the creation of chi joints, rather than signal or coding joints.

Full Text

The Full Text of this article is available as a PDF (1.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Showe LC, Croce CM. The role of chromosomal translocations in B- and T-cell neoplasia. Annu Rev Immunol. 1987;5:253–277. [PubMed]
  • Boehm T, Rabbitts TH. A chromosomal basis of lymphoid malignancy in man. Eur J Biochem. 1989 Oct 20;185(1):1–17. [PubMed]
  • McGuire EA, Hockett RD, Pollock KM, Bartholdi MF, O'Brien SJ, Korsmeyer SJ. The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein. Mol Cell Biol. 1989 May;9(5):2124–2132. [PMC free article] [PubMed]
  • Cheng JT, Yang CY, Hernandez J, Embrey J, Baer R. The chromosome translocation (11;14)(p13;q11) associated with T cell acute leukemia. Asymmetric diversification of the translocational junctions. J Exp Med. 1990 Feb 1;171(2):489–501. [PMC free article] [PubMed]
  • Tsujimoto Y, Louie E, Bashir MM, Croce CM. The reciprocal partners of both the t(14; 18) and the t(11; 14) translocations involved in B-cell neoplasms are rearranged by the same mechanism. Oncogene. 1988 Apr;2(4):347–351. [PubMed]
  • Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985 Jun 21;228(4706):1440–1443. [PubMed]
  • Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce CM. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985 Sep 27;229(4720):1390–1393. [PubMed]
  • Cleary ML, Sklar J. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439–7443. [PMC free article] [PubMed]
  • Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL, Korsmeyer SJ. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985 Jul;41(3):899–906. [PubMed]
  • Gauwerky CE, Haluska FG, Tsujimoto Y, Nowell PC, Croce CM. Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8548–8552. [PMC free article] [PubMed]
  • Bakhshi A, Wright JJ, Graninger W, Seto M, Owens J, Cossman J, Jensen JP, Goldman P, Korsmeyer SJ. Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2396–2400. [PMC free article] [PubMed]
  • Smith GR. Chi hotspots of generalized recombination. Cell. 1983 Oct;34(3):709–710. [PubMed]
  • Krowczynska AM, Rudders RA, Krontiris TG. The human minisatellite consensus at breakpoints of oncogene translocations. Nucleic Acids Res. 1990 Mar 11;18(5):1121–1127. [PMC free article] [PubMed]
  • Aisenberg AC, Wilkes BM, Jacobson JO. The bcl-2 gene is rearranged in many diffuse B-cell lymphomas. Blood. 1988 Apr;71(4):969–972. [PubMed]
  • Crescenzi M, Seto M, Herzig GP, Weiss PD, Griffith RC, Korsmeyer SJ. Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4869–4873. [PMC free article] [PubMed]
  • Ichihara Y, Matsuoka H, Kurosawa Y. Organization of human immunoglobulin heavy chain diversity gene loci. EMBO J. 1988 Dec 20;7(13):4141–4150. [PMC free article] [PubMed]
  • Cotter F, Price C, Zucca E, Young BD. Direct sequence analysis of the 14q+ and 18q- chromosome junctions in follicular lymphoma. Blood. 1990 Jul 1;76(1):131–135. [PubMed]
  • Yamada M, Wasserman R, Reichard BA, Shane S, Caton AJ, Rovera G. Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. J Exp Med. 1991 Feb 1;173(2):395–407. [PMC free article] [PubMed]
  • Ravetch JV, Siebenlist U, Korsmeyer S, Waldmann T, Leder P. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes. Cell. 1981 Dec;27(3 Pt 2):583–591. [PubMed]
  • Flanagan JG, Rabbitts TH. The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes. EMBO J. 1982;1(5):655–660. [PMC free article] [PubMed]
  • Gibbs PE, Zielinski R, Boyd C, Dugaiczyk A. Structure, polymorphism, and novel repeated DNA elements revealed by a complete sequence of the human alpha-fetoprotein gene. Biochemistry. 1987 Mar 10;26(5):1332–1343. [PubMed]
  • Chen-Levy Z, Nourse J, Cleary ML. The bcl-2 candidate proto-oncogene product is a 24-kilodalton integral-membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the t(14;18) translocation. Mol Cell Biol. 1989 Feb;9(2):701–710. [PMC free article] [PubMed]
  • Seto M, Jaeger U, Hockett RD, Graninger W, Bennett S, Goldman P, Korsmeyer SJ. Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma. EMBO J. 1988 Jan;7(1):123–131. [PMC free article] [PubMed]
  • Tutter A, Riblet R. Conservation of an immunoglobulin variable-region gene family indicates a specific, noncoding function. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7460–7464. [PMC free article] [PubMed]
  • Kenter AL, Birshtein BK. Chi, a promoter of generalized recombination in lambda phage, is present in immunoglobulin genes. Nature. 1981 Oct 1;293(5831):402–404. [PubMed]
  • Schatz DG, Oettinger MA, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell. 1989 Dec 22;59(6):1035–1048. [PubMed]
  • Siebenlist U, Ravetch JV, Korsmeyer S, Waldmann T, Leder P. Human immunoglobulin D segments encoded in tandem multigenic families. Nature. 1981 Dec 17;294(5842):631–635. [PubMed]
  • Buluwela L, Albertson DG, Sherrington P, Rabbitts PH, Spurr N, Rabbitts TH. The use of chromosomal translocations to study human immunoglobulin gene organization: mapping DH segments within 35 kb of the C mu gene and identification of a new DH locus. EMBO J. 1988 Jul;7(7):2003–2010. [PMC free article] [PubMed]
  • Seto M, Osada H, Ueda R, Ito C, Iwaki O, Oyama A, Suchi T, Takahashi T. bcl-2 translocation in Japanese B cell lymphoma: novel bcl-2 translocation with immunoglobulin heavy chain diversity segment. Jpn J Cancer Res. 1991 Jan;82(1):65–71. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • Nucleotide
    Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...