Fig. 3.
Fig. 3. The t(4;14) translocation results in IgH-MMSET hybrid transcripts. (A) The top diagram shows the genomic organization of the IgH locus on 14q32 in an IgG isotype switched plasma cell. The structural elements include the recombined VDJ exons, 5′ and 3′ enhancers (Eμ and 3′E), the noncoding Ιμ (gray rectangle) and coding Cγ (white rectangle) exons, and the switch regions (circles). The transcription may initiate either from promoters (black arrowhead) upstream of JH or Iμ, in both cases with splicing to the Cγ exon. The second diagram shows the 4p16 locus, with FGFR3 on the telomeric side, and MMSET on the centromeric side. The MMSET exons are depicted as black rectangles. The main promoter upstream of exon 1 and a cryptic promoter upstream of exon 4 are depicted. The alternative splicing occurring between exon 10-11 or exon 10-12 is shown. The lower two diagrams represent the der(4) and der(14) as result of the t(4;14) translocation in JIM3 MM cell line. On der(4), the transcription may initiate at a lower level either from (VD)J or Iμ, and in both cases it splices to exon 4 of MMSET, proceeds up to exon 10 and then it splices to exon 12, but not exon 11. However, the transcription preferentially initiates from the upregulated MMSET promoter upstream of exon 4 and generates both types of alternatively spliced forms of MMSET. On the der(14), the reciprocal hybrid transcript is formed when the transcription starts from the MMSET promoter upstream of exon 1, and it splices to the Cγ exon. (B) An RT-PCR assay detects hybrid transcripts Iμ-MMSET (top panel) and JH-MMSET (middle panel) on der(4), and MMSET-Cγ (bottom panel) on der(14) in myeloma cell lines and primary tumor samples with t(4;14) translocation. The IgH exons are shaded in gray, and the MMSET exons are depicted as white rectangles. The exon structure of each hybrid transcripts is depicted and has been obtained by sequencing of the PCR product (Iμ-MMSET and MMSET-Cγ), or deduced by the size of the PCR products, consistent with the breakpoint position (JH-MMSET).

The t(4;14) translocation results in IgH-MMSET hybrid transcripts. (A) The top diagram shows the genomic organization of the IgH locus on 14q32 in an IgG isotype switched plasma cell. The structural elements include the recombined VDJ exons, 5′ and 3′ enhancers (Eμ and 3′E), the noncoding Ιμ (gray rectangle) and coding Cγ (white rectangle) exons, and the switch regions (circles). The transcription may initiate either from promoters (black arrowhead) upstream of JH or Iμ, in both cases with splicing to the Cγ exon. The second diagram shows the 4p16 locus, with FGFR3 on the telomeric side, and MMSET on the centromeric side. The MMSET exons are depicted as black rectangles. The main promoter upstream of exon 1 and a cryptic promoter upstream of exon 4 are depicted. The alternative splicing occurring between exon 10-11 or exon 10-12 is shown. The lower two diagrams represent the der(4) and der(14) as result of the t(4;14) translocation in JIM3 MM cell line. On der(4), the transcription may initiate at a lower level either from (VD)J or Iμ, and in both cases it splices to exon 4 of MMSET, proceeds up to exon 10 and then it splices to exon 12, but not exon 11. However, the transcription preferentially initiates from the upregulated MMSET promoter upstream of exon 4 and generates both types of alternatively spliced forms of MMSET. On the der(14), the reciprocal hybrid transcript is formed when the transcription starts from the MMSET promoter upstream of exon 1, and it splices to the Cγ exon. (B) An RT-PCR assay detects hybrid transcripts Iμ-MMSET (top panel) and JH-MMSET (middle panel) on der(4), and MMSET-Cγ (bottom panel) on der(14) in myeloma cell lines and primary tumor samples with t(4;14) translocation. The IgH exons are shaded in gray, and the MMSET exons are depicted as white rectangles. The exon structure of each hybrid transcripts is depicted and has been obtained by sequencing of the PCR product (Iμ-MMSET and MMSET-Cγ), or deduced by the size of the PCR products, consistent with the breakpoint position (JH-MMSET).

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