1. Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells
by James A. L. Fenton, Jan-Willem Vaandrager, Wilhelmina M. Aarts, Richard J. Bende, Karel Heering, Martin van Dijk, Gareth Morgan, Carel J. M. van Noesel, Ed Schuuring, and Philip M. Kluin
Blood
Volume 99(2):
January 15, 2002
©2002 by American Society of Hematology

2. Genomic organization of the IGH-BCL2 breakpoint.
Genomic organization of the IGH-BCL2 breakpoint. (A) Schematic demonstration of part of the germline IGH locus (IGH), the germline 5′ part of the BCL2 gene (BCL2), and the fusion product, der(18), observed in FL5094 (Fl5094). The 2 arrows indicate the position of primers used for PCR and genomic sequence analysis. (B) The sequence of the breakpoint junction and alignment with BCL2 intron 1 and germline Sμ sequences. The sequence shown is part of a 500–base pair (bp) product obtained with primers 5′-GGCAATGAGATGGCTTTAGCTG (5′Sμ forward, bp 66 through 87 Genbank X54713) and 5′-CATACACACACTACAAGTAACACGG (BCL2intron 1 reverse, bp 1072 through 1094, Genbank M ). Nucleotides 1 through 38 are homologous to bases 442 through 485 of human Sμ sequence (X54713), and nucleotides 41 through 72 are homologous to bases 1001 through 1039 of BCL2 sequence (M ) The genomic chromosomal breakpoint is located at nucleotides 41 through 42 (ct), which are common to both sequences.
James A. L. Fenton et al. Blood 2002;99:
©2002 by American Society of Hematology

3. An IGH-BCL2 hybrid transcript resulting from the t(14;18) translocation results in.(A) The top diagram shows the organization of der(18) transcript as result of the t(14;18) translocation.
An IGH-BCL2 hybrid transcript resulting from the t(14;18) translocation results in.(A) The top diagram shows the organization of der(18) transcript as result of the t(14;18) translocation. The transcription initiates from Iμ and splices to an acceptor site at exon 2 ofBCL2. There is also splicing from exon 2 to exon 3. Donor and acceptor sites between Iμ and BCL2 exon 2 boundary are shown within the boxes. The orientation of primers used for RT-PCR is shown with arrows. (B) The complementary DNA (cDNA) sequence of the breakpoint junction and alignment with germline 14q32 sequence preceeding Sμ and BCL2 cDNA sequences are shown. The sequence is part of a 1-kb product obtained with primers 5′-AGCCCTTGTTAATGGACTTGGAGG (5′Iμ forward, Genbank X97051, bp through 91652) and 5′-CAGATAGGCACCCAGGGTGAT (BCL2 exon 3, reverse Genbank M , bp 2146 through 2167). The relative location of these primers is represented by arrows in panel A. Nucleotides 1 through 78 are homologous to bases of 14q32 sequence (X97051) located 5′ of Sμ in germline DNA. Nucleotides 78 through 166 are homologous to bases 1172 through 1260 of BCL2 sequence (M ). The breakpoint on 14q32 is located 30 bp beyond a known HindIII site (shown) preceding the Sμ sequence. The remaining parts of the splice donor and acceptor sites are underlined.
James A. L. Fenton et al. Blood 2002;99:
©2002 by American Society of Hematology