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Blood, 1 August 2004, Vol. 104, No. 3, pp. 904-905. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hirt, C. Articles by Dölken, G. Search for Related Content PubMed PubMed Citation Articles by Hirt, C. Articles by Dölken, G. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE To the editor: Low prevalence of circulating t(11;14)(q13;q32)–positive cells in the peripheral blood of healthy individuals as detected by real-time quantitative PCR The characteristic chromosomal translocation of follicular lymphoma, the t(14;18)(q32;q21), has also been detected at high prevalence and frequency in circulating B cells in healthy individuals.1-3 Since both the t(14;18) and the t(11;14)(q13;q32) translocations are thought to be generated by a common mechanism at at least one site, the VDJ recombinase,4 we determined the prevalence of t(11;14)–as well as t(14;18)–positive cells in the peripheral blood of 100 healthy individuals by real-time quantitative polymerase chain reaction (PCR). The PCR for the detection of the BCL-2/IgH rearrangement has previously been described.5 The t(11;14) translocation was analyzed using the same JH-consensus primer in combination with a BCL-1 primer 5'-GATAAAGGCGAGGAGCAT-3' and a BCL-1 probe 5'-TAACCGAATATGCAGTGCAGCAATT-3'. At least 5 replicates of 1 µg DNA isolated from peripheral blood mononuclear cells (PBMNCs) were tested for the presence of each translocation. The total number of cells tested was determined by quantitative PCR using k-ras as reference gene. In spiking experiments, a single t(11;14)–positive JVM-2 cell diluted in 250 000 t(11;14)–negative cells could be consistently detected. Circulating t(11;14)–positive cells were detected in only one of the 100 healthy individuals at a frequency of 0.6 t(11;14) copies/105 PBMNCs (Table 1). The translocation fragments amplified from the t(11;14)–positive healthy individual HI65, from the JVM-2 cell line, and from all t(11;14)–PCR–positive patients with mantle cell lymphoma (MCL) ever tested in our laboratory were sequenced. All nucleotide sequences showed a unique and distinct combination of BCL-1 breakpoint, N-nucleotides, and JH breakpoint (Table 2). The sequence analysis failed in one patient (MCL8). However, the length of the t(11;14) fragment, of about 180 bp, amplified from this patient compared with the one of the healthy individual HI65, of 281 bp (Figure 1), makes a false-positive result due to contamination very unlikely. PBMNC samples of the t(11;14)–positive healthy individual (HI65) obtained 2 years before and 3 years after the t(11;14)–positive sample were negative by t(11;14)–PCR. View this table: [in this window] [in a new window]   Table 1.. Circulating t(11;14)– and t(14;18)–positive cells   View this table: [in this window] [in a new window]   Table 2.. Nucleotide sequence data of all t(11;14) PCR fragments amplified in this study and ever in our laboratory   View larger version (52K): [in this window] [in a new window]   Figure 1.. Agarose-gel electrophoresis of all t(11;14) PCR fragments amplified in this study and ever in our laboratory. Gel electrophoresis of all t(11;14) fragments amplified by PCR. Lanes 1 and 12: 100 bp molecular weight marker (M); lane 2: HI 65; lane 3: JVM-2; lanes 4-11: MCL1-8.   In contrast to the very low prevalence of t(11;14)–positive cells, 39 (45%) of 86 individuals were t(14;18)–positive, comparable to earlier results.1-3 Since the DNA breaks at the IgH locus are mediated in both translocations by the VDJ recombinase, the markedly different prevalence of circulating t(11;14)– and t(14;18)–positive cells in healthy individuals could be explained by different frequencies of DNA breaks occurring within the BCL-1 and the BCL-2 gene. In addition, the clonal expansion of the translocation-carrying cells, which is necessary for detection in the peripheral blood by PCR, may be influenced by variable degrees of proliferative potential of the affected cells and the different susceptibility to immunologic control mechanisms. Moreover, the acquisition of the t(14;18) translocation may be regarded as the first step in the development of follicular lymphoma,6 whereas in mantle cell lymphoma there is some evidence that the t(11;14) translocation might be preceded by alterations affecting the genomic stability, such as mutations or deletions of the ATM gene.7,8 If an impaired genomic stability is a prerequisite for the formation of the t(11;14) translocation, the prevalence of t(11;14)–positive cells in the peripheral blood of healthy individuals would be expected to be very low. Carsten Hirt, Frank Schüler, Lars Dölken, Christian A. Schmidt, and Gottfried Dölken Correspondence: Gottfried Dölken, Department of Hematology and Oncology, University Medical Center, Ernst-Moritz-Arndt-University Greifswald, Sauerbruchstrasse, D-17487 Greifswald, Germany; e-mail: doelken{at}uni-greifswald.de. References Liu Y, Hernandez AM, Shibata D, Cortopassi GA. BCL2 translocation frequency rises with age in humans. Proc Natl Acad Sci U S A. 1994;91: 8910-8914.[Abstract/Free Full Text] Dölken G, Illerhaus G, Hirt C, Mertelsmann R. BCL-2/JH-rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases. J Clin Oncol. 1996;14: 1333-1344.[Abstract/Free Full Text] Schüler F, Hirt C, Dölken G. Chromosomal translocation t(14;18) in healthy individuals. Semin Cancer Biol. 2003;13: 203-209.[CrossRef][Medline] [Order article via Infotrieve] Marculescu R, Le T, Simon P, Jaeger U, Nadel B. V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. J Exp Med. 2002;195: 85-98.[Abstract/Free Full Text] Dölken L, Schüler F, Dölken G. Quantitative detection of t(14;18)-positive cells by real-time quantitative PCR using fluorogenic probes. BioTechniques. 1998;25: 1058-1064.[Medline] [Order article via Infotrieve] Dölken G. Detection of minimal residual disease. Adv Cancer Res. 2001;82: 133-185.[Medline] [Order article via Infotrieve] Bishop AJ, Barlow C, Wynshaw-Boris AJ, Schiestl RH. ATM deficiency causes an increased frequency of intrachromosomal homologous recombination in mice. Cancer Res. 2000;60: 395-399.[Abstract/Free Full Text] Stilgenbauer S, Winkler D, Ott G, et al. Molecular characterization of 11q deletions points to a pathogenic role of the ATM gene in mantle cell lymphoma. Blood. 1999;94: 3262-3264.[Abstract/Free Full Text] Rimokh R, Berger F, Delsol G, et al. Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas. Blood. 2003;83: 1871-1875. Ravetch JV, Siebenlist U, Korsmeyer S, Waldman T, Leder P. Structure of the human immunoglobulin mu locus: characterization of embryonic and rear-ranged J and D genes. Cell. 1981;27: 583-591.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Bea, I. Salaverria, L. Armengol, M. Pinyol, V. Fernandez, E. M. Hartmann, P. Jares, V. Amador, L. Hernandez, A. Navarro, et al. Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling Blood, March 26, 2009; 113(13): 3059 - 3069. [Abstract] [Full Text] [PDF] S. Janz Genetic and Environmental Cofactors of Myc Translocations in Plasma Cell Tumor Development in Mice J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 37 - 40. 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